Trial Outcomes & Findings for Upfront Chimeric Antigen Receptor T-Cell to Upgrade Response in Multiple Myeloma (NCT NCT05032820)
NCT ID: NCT05032820
Last Updated: 2026-05-19
Results Overview
Achieving a complete response or better (CR or sCR) as assessed by the 6-month time point after BCMA CAR T-cell therapy in MM patients with suboptimal disease responses after an autologous HCT and lenalidomide maintenance.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
40 participants
Primary outcome timeframe
6 months
Results posted on
2026-05-19
Participant Flow
BMT CTN 1902's enrollment was between January 2022 and December 2023 with 40 participants enrolled from 12 centers. The study opened to accrual in February 2021. Fifteen centers were activated for enrollment. The study closed to accrual on January 09, 2024.
There was a Safety Run-in that included the first three participants enrolled on the study with staggered enrollment to assess for excess early toxicity. These data were reviewed and enrollment was approved in the Continuing Enrollment Phase which began on October 14, 2022.
Participant milestones
| Measure |
Lenalidomide and bb2121
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Overall Study
STARTED
|
40
|
|
Overall Study
COMPLETED
|
38
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Lenalidomide and bb2121
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
This row is only for infused patients and therefore has less participants in this row than others as not all enrolled participants were infused.
Baseline characteristics by cohort
| Measure |
Lenalidomide and bb2121
n=40 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Age, Continuous
|
61.2 years
STANDARD_DEVIATION 7.72 • n=38 Participants • This row is only for infused patients and therefore has less participants in this row than others as not all enrolled participants were infused.
|
|
Sex: Female, Male
Female
|
11 Participants
n=40 Participants
|
|
Sex: Female, Male
Male
|
29 Participants
n=40 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=40 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
34 Participants
n=40 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=40 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=40 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=40 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=40 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=40 Participants
|
|
Race (NIH/OMB)
White
|
29 Participants
n=40 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=40 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=40 Participants
|
|
Karnofsky Performance Score
70 or 80
|
17 Participants
n=40 Participants
|
|
Karnofsky Performance Score
90 or 100
|
23 Participants
n=40 Participants
|
|
Multiple Myeloma Paraprotein Type
IgA Kappa
|
2 Participants
n=40 Participants
|
|
Multiple Myeloma Paraprotein Type
IgA Lambda
|
2 Participants
n=40 Participants
|
|
Multiple Myeloma Paraprotein Type
IgG Kappa
|
20 Participants
n=40 Participants
|
|
Multiple Myeloma Paraprotein Type
IgG Lamda
|
6 Participants
n=40 Participants
|
|
Multiple Myeloma Paraprotein Type
Kappa light chain
|
8 Participants
n=40 Participants
|
|
Multiple Myeloma Paraprotein Type
Lambda light chain
|
2 Participants
n=40 Participants
|
|
ISS Stage at Diagnosis
I
|
14 Participants
n=40 Participants
|
|
ISS Stage at Diagnosis
II
|
18 Participants
n=40 Participants
|
|
ISS Stage at Diagnosis
III
|
6 Participants
n=40 Participants
|
|
ISS Stage at Diagnosis
Unknown
|
2 Participants
n=40 Participants
|
|
R-ISS Stage at Diagnosis
I
|
11 Participants
n=40 Participants
|
|
R-ISS Stage at Diagnosis
II
|
20 Participants
n=40 Participants
|
|
R-ISS Stage at Diagnosis
III
|
2 Participants
n=40 Participants
|
|
R-ISS Stage at Diagnosis
Unknown
|
7 Participants
n=40 Participants
|
|
Cytogenetics
High risk
|
9 Participants
n=40 Participants
|
|
Cytogenetics
No abnormalities
|
7 Participants
n=40 Participants
|
|
Cytogenetics
Standard risk
|
23 Participants
n=40 Participants
|
|
Cytogenetics
Unknown
|
1 Participants
n=40 Participants
|
|
Myeloma Risk Status
High risk
|
12 Participants
n=40 Participants
|
|
Myeloma Risk Status
Standard risk
|
28 Participants
n=40 Participants
|
|
Number of Lines of Initial Systemic Anti-Myeloma Therapy
1 Line
|
32 Participants
n=40 Participants
|
|
Number of Lines of Initial Systemic Anti-Myeloma Therapy
2 Lines
|
6 Participants
n=40 Participants
|
|
Number of Lines of Initial Systemic Anti-Myeloma Therapy
3 Lines
|
2 Participants
n=40 Participants
|
|
Disease Status Prior to Transplant
VGPR
|
7 Participants
n=40 Participants
|
|
Disease Status Prior to Transplant
PR
|
30 Participants
n=40 Participants
|
|
Disease Status Prior to Transplant
SD
|
3 Participants
n=40 Participants
|
|
Disease Status Prior to Enrollment
VGPR
|
22 Participants
n=40 Participants
|
|
Disease Status Prior to Enrollment
PR
|
17 Participants
n=40 Participants
|
|
Disease Status Prior to Enrollment
MR
|
1 Participants
n=40 Participants
|
|
Disease Status at LD Chemotherapy Initiation
VGPR
|
22 Participants
n=40 Participants
|
|
Disease Status at LD Chemotherapy Initiation
PR
|
13 Participants
n=40 Participants
|
|
Disease Status at LD Chemotherapy Initiation
MR
|
1 Participants
n=40 Participants
|
|
Disease Status at LD Chemotherapy Initiation
Missing
|
2 Participants
n=40 Participants
|
|
Disease Status at LD Chemotherapy Initiation
No LD Chemotherapy
|
2 Participants
n=40 Participants
|
|
Interval from Diagnosis of Symptomatic Multiple Myeloma to Transplant
|
7.1 months
STANDARD_DEVIATION 2.34 • n=40 Participants
|
|
interval from diagnosis of symptomatic Multiple Myeloma to enrollment
|
16.2 months
STANDARD_DEVIATION 2.77 • n=40 Participants
|
|
Interval from Transplant to Enrollment
|
9.1 months
STANDARD_DEVIATION 1.68 • n=40 Participants
|
PRIMARY outcome
Timeframe: 6 monthsPopulation: Patients who received BCMA CAR T-Cell Therapy
Achieving a complete response or better (CR or sCR) as assessed by the 6-month time point after BCMA CAR T-cell therapy in MM patients with suboptimal disease responses after an autologous HCT and lenalidomide maintenance.
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Efficacy of BCMA CAR-T Cell Therapy
Acheived CR/sCR by 6 Months post Infusion
|
25 Participants
|
|
Efficacy of BCMA CAR-T Cell Therapy
Did Not Acheive CR/sCR by 6 Months post Infusion
|
13 Participants
|
SECONDARY outcome
Timeframe: 1 YearPopulation: Participants who received an infusion
Diseases will be assessed by response categories based on the International Myeloma Working Group: Stringent Complete Response (sCR), Complete Remission (CR), Very Good Partial Remission (VGPR), Partial Remission (PR), Minimal Response (MR), Stable Disease (SD).
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Cumulative Incidence of Disease Progression
|
2.6 Percent probability
Interval 0.3 to 9.9
|
SECONDARY outcome
Timeframe: 1 YearPopulation: Participants who received an infusion
Proportion of patients achieving upgrade in response following enrollment (SD to MR or greater, MR to PR or greater, or PR to VGPR or greater) and Conversion to MRD negativity. MRD will be assessed by multi-color flow at 10-5 level
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Proportion of Patients Achieving an Upgrade in Response Based on Their Best Disease Response
|
34 Participants
|
SECONDARY outcome
Timeframe: 1 YearPopulation: Participants who received an infusion
Non-Relapse Mortality (NRM) is defined as death occurring in a patient from causes other than disease relapse or progression. Disease progression is the competing event for NRM.
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Number of Participants With Non Relapse Mortality
|
0 Participants
|
SECONDARY outcome
Timeframe: 1 YearPopulation: Participants who received an infusion
Defined as progression of disease or death from any cause. Surviving patients without disease progression will be censored at the date of last contact.
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Kaplan-Meier of Progression Free Survival
|
97.4 Percent probability
Interval 87.1 to 99.5
|
SECONDARY outcome
Timeframe: Day 4, Day 7, Day 10, Day 14, and Day 21 post-infusionPopulation: Participants who received an infusion
Overall incidence of CRS of any grade and grade 3 or 4 CRS post CAR T-cell infusion will be reported on all patients.
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 21 · Grade 3
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 21 · Grade 4
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 21 · Grade 5
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 21 · No CRS
|
38 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 14 · Grade 2
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 14 · Grade 3
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 14 · Grade 4
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 14 · Grade 5
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 14 · No CRS
|
38 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 10 · Grade 1
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 21 · Grade 1
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 21 · Grade 2
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 14 · Grade 1
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 4 · Grade 1
|
25 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 4 · Grade 2
|
5 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 4 · Grade 3
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 4 · Grade 4
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 4 · Grade 5
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 4 · No CRS
|
8 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 7 · Grade 1
|
8 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 7 · Grade 2
|
1 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 7 · Grade 3
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 7 · Grade 4
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 7 · Grade 5
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 7 · No CRS
|
29 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 10 · Grade 2
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 10 · Grade 3
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 10 · Grade 4
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 10 · Grade 5
|
0 Participants
|
|
Incidence of Cytokine Release Syndrome (CRS)
Day 10 · No CRS
|
38 Participants
|
SECONDARY outcome
Timeframe: 1 YearPopulation: Participants who received an infusion
Overall incidence of prolonged cytopenias will be reported. Prolonged cytopenia is defined as failure to achieve ANC greater than 500/mm3 or platelet count greater than 20,000/mm3(with or without support) by 30 days post CAR T-cell infusion.
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Incidence of Prolonged Cytopenias
|
0 Participants
|
SECONDARY outcome
Timeframe: 1 YearPopulation: Participants who received an infusion
Overall incidence of CAR T-cell related neurotoxicity per the ASBMT immune effector cell associated neurotoxicity syndrome (ICANS) Consensus Grading.
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Incidence of Neurotoxicity
|
0 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 yearPopulation: Participants who received an infusion
All Grade 3 or higher toxicities will be tabulated. The proportion of patients experiencing cytokine release syndrome CRS will be reported including overall and grades 3-4 based on the ASTCT grading
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Exploratory Objective 1: Incidence of Toxicities Greater Than or Equal to Grade 3 Per the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
|
22 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 YearPopulation: Participants who received an infusion
incidence of definite and probable viral, fungal and bacterial infections will be tabulated for each patient
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Exploratory Objective 2: Incidence of Infections Per Protocol-specific Manual of Procedures (MOP)
|
12 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 YearPopulation: Participants who received an infusion
The feasibility of resuming maintenance following enrollment by 180 days after CAR T-cell infusion will be described. The proportion of patients initiating maintenance at 180 days following bb2121 infusion will be reported.
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Exploratory Objective 3: Incidence of Re-initiation of Lenalidomide Maintenance
|
38 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 YearPopulation: Participants who received an infusion
The event is death from any cause. The time to this event is the time from initial enrollment to death, loss to follow-up, or the end of the study, whichever comes first.
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Exploratory Objective 2: Number of Participants Who Did Not Die (Overall Survival)
|
38 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: pre-LD chemo, day 4, 7, 14, 21, 30, 60, 90, 180, 270, 365Population: Participants who received an infusion
Quantitation of CAR T-cells in peripheral blood will be determined at specified timepoints by quantitative PCR assay, measured in copies/mcg genomic DNA.
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Exploratory Objective 2: Summary Statistics of CAR T-cell Expansion
Day 7
|
99960.98 CAR T-cells (copies/mcg DNA)
Standard Deviation 100449.434
|
|
Exploratory Objective 2: Summary Statistics of CAR T-cell Expansion
Day 14
|
46586.56 CAR T-cells (copies/mcg DNA)
Standard Deviation 180377.654
|
|
Exploratory Objective 2: Summary Statistics of CAR T-cell Expansion
Day 21
|
16290.81 CAR T-cells (copies/mcg DNA)
Standard Deviation 86387.497
|
|
Exploratory Objective 2: Summary Statistics of CAR T-cell Expansion
Day 30
|
7249.38 CAR T-cells (copies/mcg DNA)
Standard Deviation 53549.080
|
|
Exploratory Objective 2: Summary Statistics of CAR T-cell Expansion
Day 60
|
567.88 CAR T-cells (copies/mcg DNA)
Standard Deviation 18645.673
|
|
Exploratory Objective 2: Summary Statistics of CAR T-cell Expansion
Day 90
|
251.52 CAR T-cells (copies/mcg DNA)
Standard Deviation 11118.975
|
|
Exploratory Objective 2: Summary Statistics of CAR T-cell Expansion
Day 180
|
90.52 CAR T-cells (copies/mcg DNA)
Standard Deviation 2414.251
|
|
Exploratory Objective 2: Summary Statistics of CAR T-cell Expansion
Day 270
|
64.81 CAR T-cells (copies/mcg DNA)
Standard Deviation 1346.240
|
|
Exploratory Objective 2: Summary Statistics of CAR T-cell Expansion
Day 365
|
41.26 CAR T-cells (copies/mcg DNA)
Standard Deviation 626.792
|
|
Exploratory Objective 2: Summary Statistics of CAR T-cell Expansion
Pre-LD chemo
|
0.00 CAR T-cells (copies/mcg DNA)
Standard Deviation 0.000
|
|
Exploratory Objective 2: Summary Statistics of CAR T-cell Expansion
Day 4
|
5271.59 CAR T-cells (copies/mcg DNA)
Standard Deviation 14554.838
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 monthsPopulation: Participants who received an infusion
Quantitation of CAR T-cells in peripheral blood will be determined at specified timepoints by quantitative PCR assay, measured in copies/mcg genomic DNA. Peak CAR T-cell expansion will be compared between subjects who are and are not in CR at 6 months.
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Exploratory Objective 2: Peak CAR T-cell Expansion
In CR/sCR at 6 mth
|
110502.71 copies/mcg DNA
Standard Deviation 102932.728
|
|
Exploratory Objective 2: Peak CAR T-cell Expansion
Not in CR/sCR at 6 mth
|
101723.96 copies/mcg DNA
Standard Deviation 272376.464
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 6 months, 1 YearPopulation: Participants who received and infusion
Quantitation of CAR T-cells in peripheral blood will be determined at specified timepoints by quantitative PCR assay, measured in copies/mcg genomic DNA. Persistence will be measured in 2 ways: 1) as an area under the curve (AUC) over first 6 months post CAR T-cell infusion; and 2) as still having detectable CAR T-cells at 6 months post CAR T-cell infusion. AUC6mos and 6-month persistence will be compared between subjects who are and are not in CR at 6 months and 12 months.
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Exploratory Objective 2: CAR T-cell Persistence Area Under the Curve Over the First 6 Months Post CAR T-cell Infusion
In CR/sCR at 6 mth
|
1811283.45 months*(copies/mcg of DNA)
Standard Deviation 1649413.714
|
|
Exploratory Objective 2: CAR T-cell Persistence Area Under the Curve Over the First 6 Months Post CAR T-cell Infusion
Not in CR/sCR at 6 mth
|
1156887.25 months*(copies/mcg of DNA)
Standard Deviation 6810471.278
|
|
Exploratory Objective 2: CAR T-cell Persistence Area Under the Curve Over the First 6 Months Post CAR T-cell Infusion
In CR/sCR at 12 mth
|
1811283.45 months*(copies/mcg of DNA)
Standard Deviation 4757894.776
|
|
Exploratory Objective 2: CAR T-cell Persistence Area Under the Curve Over the First 6 Months Post CAR T-cell Infusion
Not in CR/sCR at 12 mth
|
1019484.20 months*(copies/mcg of DNA)
Standard Deviation 1535876.342
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 1 YearBCMA expression at specified timepoints will be determined by immunohistochemical staining of bone marrow biopsy specimens and/or flow cytometric analysis of bone marrow aspirate material, in order to assess for baseline expression and potential loss of expression post-treatment. Both percent of MM cells that stain positive as well as staining intensity will be reported.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: Pre-LD chemo, Day 30, 90, 180, 365Population: Participants who received an infusion
The cellular composition of marrow (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC) will be quantified at the specified timepoints by flow cytometry.
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
Monocytes day 180
|
9.35 % BMMC
Standard Deviation 5.27
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
Monocytes day 365
|
6.64 % BMMC
Standard Deviation 6.32
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
gMDSC pre-LD chemo
|
0.03 % BMMC
Standard Deviation 0.06
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
gMDSC day 30
|
0.05 % BMMC
Standard Deviation 0.13
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
gMDSC day 90
|
0.02 % BMMC
Standard Deviation 0.17
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
gMDSC day 180
|
0.05 % BMMC
Standard Deviation 0.13
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
gMDSC day 365
|
0.03 % BMMC
Standard Deviation 0.16
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
mMDSC pre-LD chemo
|
0.04 % BMMC
Standard Deviation 0.14
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
mMDSC day 30
|
0.07 % BMMC
Standard Deviation 0.17
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
mMDSC day 90
|
0.11 % BMMC
Standard Deviation 0.32
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
mMDSC day 180
|
0.05 % BMMC
Standard Deviation 0.18
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
mMDSC day 365
|
0.16 % BMMC
Standard Deviation 0.20
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
B cells pre-LD chemo
|
9.82 % BMMC
Standard Deviation 6.24
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
B cells Day 30
|
3.17 % BMMC
Standard Deviation 4.70
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
B cells Day 90
|
7.81 % BMMC
Standard Deviation 9.12
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
B cells Day 180
|
7.13 % BMMC
Standard Deviation 5.09
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
B cells Day 365
|
4.47 % BMMC
Standard Deviation 4.99
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
T cells pre-LD chemo
|
27.81 % BMMC
Standard Deviation 17.43
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
T cells day 30
|
25.68 % BMMC
Standard Deviation 17.38
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
T cells day 90
|
25.37 % BMMC
Standard Deviation 17.75
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
T cells day 180
|
32.84 % BMMC
Standard Deviation 16.62
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
T cells day 365
|
19.49 % BMMC
Standard Deviation 17.16
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
Monocytes pre-LD chemo
|
9.08 % BMMC
Standard Deviation 4.31
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
Monocytes day 30
|
13.52 % BMMC
Standard Deviation 8.21
|
|
Exploratory Objective 2: Immune Reconstitution (B-Cells, T-Cells, Monocytes, gMDSC, mMDSC)
Monocytes day 90
|
7.99 % BMMC
Standard Deviation 9.54
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Pre-LD chemo, Day 30, 90, 180, 365Population: Participants who received an infusion
The cellular composition of marrow (WBC Count) will be quantified at the specified timepoints by flow cytometry.
Outcome measures
| Measure |
Lenalidomide and bb2121
n=38 Participants
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Exploratory Objective 2: Immune Reconstitution (WBC)
WBC count pre-LD chemo
|
10.69 x10^3 cells/uL
Standard Deviation 15.61
|
|
Exploratory Objective 2: Immune Reconstitution (WBC)
WBC count day 30
|
6.09 x10^3 cells/uL
Standard Deviation 8.43
|
|
Exploratory Objective 2: Immune Reconstitution (WBC)
WBC count day 90
|
7.61 x10^3 cells/uL
Standard Deviation 15.22
|
|
Exploratory Objective 2: Immune Reconstitution (WBC)
WBC count day 180
|
6.11 x10^3 cells/uL
Standard Deviation 5.75
|
|
Exploratory Objective 2: Immune Reconstitution (WBC)
WBC count day 365
|
6.96 x10^3 cells/uL
Standard Deviation 11.61
|
Adverse Events
Lenalidomide and bb2121
Serious events: 9 serious events
Other events: 38 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Lenalidomide and bb2121
n=40 participants at risk
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Infections and infestations
Pneumonia
|
5.0%
2/40 • Number of events 2 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Infections and infestations
Pyelonephritis
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Nervous system disorders
Transient ischaemic attack
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Hepatobiliary disorders
Bile duct stone
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Immune system disorders
Cytokine Release Syndrome
|
12.5%
5/40 • Number of events 5 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
Other adverse events
| Measure |
Lenalidomide and bb2121
n=40 participants at risk
Patients complete apheresis and proceed to lymphodepleting chemotherapy with cyclophosphamide 300mg/m\^2 and fludarabine 30mg/m\^2 for 3 consecutive days followed by the infusion of BCMA CAR T-cells at a target dose of 450 x10\^6 cells. Maintenance lenalidomide, starting at 5mg a day for 21 days of a 28-day cycle will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the patient reaches 12 months post CAR T-cell infusion and continue free of progression.
Lenalidomide: Maintenance lenalidomide, starting at 5 mg a day for 21 days of a 28-day cycle, will be initiated at a minimum of at least 30 days, but no later than 180 days after the CAR T-cell infusion and will continue until the participant reaches 12 months post CAR T-cell infusion and continues free of progression
bb2121: Participants receive infusion of BCMA CAR T-cells at a target dose of 450 x 10\^6 cells.
Cyclophosphamide: 300 mg/m\^2/day for 3 consecutive days prior to the CAR T infusion
Fludarabine: 30 mg/m\^2/day or 3 consecutive days prior to the CAR T infusion
leukapheresis: Placement of central line catheter and leukapheresis
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Renal and urinary disorders
Acute kidney injury
|
5.0%
2/40 • Number of events 2 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Investigations
Alanine aminotransferase increased
|
7.5%
3/40 • Number of events 3 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Investigations
Aspartate aminotransferase increased
|
5.0%
2/40 • Number of events 2 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Investigations
Blood alkaline phosphatase
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Infections and infestations
COVID-19
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Nervous system disorders
Cognitive disorder
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Gastrointestinal disorders
Constipation
|
12.5%
5/40 • Number of events 9 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Injury, poisoning and procedural complications
Contusion
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Skin and subcutaneous tissue disorders
Dermal cyst
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Gastrointestinal disorders
Diarrhoea
|
10.0%
4/40 • Number of events 5 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Nervous system disorders
Dizziness
|
5.0%
2/40 • Number of events 2 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Nervous system disorders
Dysgeusia
|
5.0%
2/40 • Number of events 2 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Vascular disorders
Embolism
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Gastrointestinal disorders
Flatulence
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Nervous system disorders
Headache
|
7.5%
3/40 • Number of events 3 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Vascular disorders
Hypertension
|
15.0%
6/40 • Number of events 10 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
7.5%
3/40 • Number of events 5 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
5.0%
2/40 • Number of events 2 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Vascular disorders
Hypotension
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
General disorders
Influenza like illness
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
General disorders
Injection site reaction
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Injury, poisoning and procedural complications
Limb injury
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Investigations
Lymphocyte count decreased
|
85.0%
34/40 • Number of events 129 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Gastrointestinal disorders
Nausea
|
7.5%
3/40 • Number of events 3 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Investigations
Neutrophil count decreased
|
77.5%
31/40 • Number of events 98 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
General disorders
Pain
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Gastrointestinal disorders
Pancreatitis
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Investigations
Platelet count decreased
|
7.5%
3/40 • Number of events 6 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Infections and infestations
Pyelonephritis acute
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
General disorders
Pyrexia
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Infections and infestations
Respiratory syncytial virus infection
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Respiratory, thoracic and mediastinal disorders
Sinus pain
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Cardiac disorders
Sinus tachycardia
|
5.0%
2/40 • Number of events 3 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Infections and infestations
Sinusitis
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Blood and lymphatic system disorders
Thrombotic microangiopathy
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Infections and infestations
Upper respiratory tract infection
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Respiratory, thoracic and mediastinal disorders
Upper-airway cough syndrome
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Investigations
White blood cell decreased
|
72.5%
29/40 • Number of events 65 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Gastrointestinal disorders
Dyspepsia
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Blood and lymphatic system disorders
Leukocytosis
|
2.5%
1/40 • Number of events 2 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Nervous system disorders
Paraesthesia
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
5.0%
2/40 • Number of events 2 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Skin and subcutaneous tissue disorders
Rash
|
5.0%
2/40 • Number of events 2 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
Endocrine disorders
Hyperthyroidism
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
|
General disorders
Oedema
|
2.5%
1/40 • Number of events 1 • All SAEs and AEs were collected from enrollment to study completion, or for 12 months after bb2121 infusion.
Adverse events are collected on the adverse event form, toxicity form, and myelotoxicity form.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place