Trial Outcomes & Findings for Panobinostat, Carfilzomib, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma (NCT NCT03256045)
NCT ID: NCT03256045
Last Updated: 2022-05-09
Results Overview
Assessed using the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma. Key: 1 = very good partial response (VGPR); 2 = partial response (PR); 3 = minimal response (MR); 4 = stable disease (SD); 5 = progressive disease (PD). Please see IC50 and CI results in the other primary outcome measures.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
9 participants
Primary outcome timeframe
14 months
Results posted on
2022-05-09
Participant Flow
Participant milestones
| Measure |
Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone
Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Overall Study
STARTED
|
9
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Panobinostat, Carfilzomib, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Baseline characteristics by cohort
| Measure |
Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone
n=9 Participants
Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Age, Customized
|
67 years
n=99 Participants
|
|
Sex/Gender, Customized
Male
|
6 Participants
n=99 Participants
|
|
Sex/Gender, Customized
Female
|
3 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
8 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Prior therapy regimes
|
5 number of regimens
n=99 Participants
|
|
Prior autologous transplant
|
88.9 percentage of participants
n=99 Participants
|
|
Revised ISS Stage
|
2.5 ISS Stage
n=99 Participants
|
PRIMARY outcome
Timeframe: 14 monthsAssessed using the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma. Key: 1 = very good partial response (VGPR); 2 = partial response (PR); 3 = minimal response (MR); 4 = stable disease (SD); 5 = progressive disease (PD). Please see IC50 and CI results in the other primary outcome measures.
Outcome measures
| Measure |
Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone
n=9 Participants
Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Best Overall Response, by Subject
Subject MM-82
|
4 IMWG Uniform Response Grade
|
|
Best Overall Response, by Subject
Subject MM-91
|
2 IMWG Uniform Response Grade
|
|
Best Overall Response, by Subject
Subject MM-92
|
2 IMWG Uniform Response Grade
|
|
Best Overall Response, by Subject
Subject MM-95
|
1 IMWG Uniform Response Grade
|
|
Best Overall Response, by Subject
Subject MM-96
|
1 IMWG Uniform Response Grade
|
|
Best Overall Response, by Subject
Subject MM-98
|
1 IMWG Uniform Response Grade
|
|
Best Overall Response, by Subject
Subject MM-99
|
3 IMWG Uniform Response Grade
|
|
Best Overall Response, by Subject
Subject MM-109
|
4 IMWG Uniform Response Grade
|
|
Best Overall Response, by Subject
Subject M-111
|
1 IMWG Uniform Response Grade
|
PRIMARY outcome
Timeframe: At baselineMultiple myeloma cells are added to assay with panobinostat. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells. Results are reported in concentrations E-9.
Outcome measures
| Measure |
Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone
n=9 Participants
Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Panobinostat, by Subject
Subject MM-82
|
3.8 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Panobinostat, by Subject
Subject MM-91
|
5.9 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Panobinostat, by Subject
Subject MM-92
|
2.6 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Panobinostat, by Subject
Subject MM-95
|
19.8 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Panobinostat, by Subject
Subject MM-96
|
1.3 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Panobinostat, by Subject
Subject MM-98
|
4.4 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Panobinostat, by Subject
Subject MM-99
|
8.5 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Panobinostat, by Subject
Subject MM-109
|
13.6 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Panobinostat, by Subject
Subject MM-111
|
2.0 nM
|
PRIMARY outcome
Timeframe: At baselineMultiple myeloma cells are added to assay with carfilzomib. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells.
Outcome measures
| Measure |
Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone
n=9 Participants
Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Carfilzomib, by Subject
Subject MM-82
|
17.5 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Carfilzomib, by Subject
Subject MM-91
|
0.479 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Carfilzomib, by Subject
Subject MM-92
|
0.03 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Carfilzomib, by Subject
Subject MM-95
|
0.269 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Carfilzomib, by Subject
Subject MM-96
|
0.0048 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Carfilzomib, by Subject
Subject MM-98
|
0.159 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Carfilzomib, by Subject
Subject MM-99
|
0.159 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Carfilzomib, by Subject
Subject MM-109
|
0.108 nM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Carfilzomib, by Subject
Subject MM-111
|
0.0152 nM
|
PRIMARY outcome
Timeframe: At baselinePopulation: Results for subject MM-92 were not reported.
Multiple myeloma cells are added to assay with dexamethasone. Cell viability and IC50 is determined. IC50 is the inhibitory concentration that kills 50% of cells. Results are reported in concentrations E-6.
Outcome measures
| Measure |
Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone
n=8 Participants
Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Dexamethasone, by Subject
Subject MM-82
|
3.7 uM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Dexamethasone, by Subject
Subject MM-91
|
10.9 uM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Dexamethasone, by Subject
Subject MM-95
|
7 uM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Dexamethasone, by Subject
Subject MM-96
|
1.1 uM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Dexamethasone, by Subject
Subject MM-98
|
14.8 uM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Dexamethasone, by Subject
Subject MM-99
|
8.6 uM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Dexamethasone, by Subject
Subject MM-109
|
80 uM
|
|
Multiple Myeloma Cells In-vitro Drug Sensitivity to Dexamethasone, by Subject
Subject MM-111
|
1.1 uM
|
PRIMARY outcome
Timeframe: At baselinePopulation: CI score was not reported for subject MM-82.
Concentration of carfilzomib and panobinostat in combination leading to 90% growth inhibition of multiple myeloma cells in-vitro. The combination index (CI) is calculated using formula: CI = (\[D1\] in the combination / \[D1\] alone) + (\[D2\] in the combination / \[D2\] alone). Key: CI = 1 no synergy; CI\<1 synergy; CI\>1 antagonism.
Outcome measures
| Measure |
Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone
n=8 Participants
Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Synergy of Panobinostat and Carfilzomib in Combination, Per Subject.
Subject MM-91
|
2.5 Combination index
|
|
Synergy of Panobinostat and Carfilzomib in Combination, Per Subject.
Subject MM-92
|
2.4 Combination index
|
|
Synergy of Panobinostat and Carfilzomib in Combination, Per Subject.
Subject MM-95
|
0.3 Combination index
|
|
Synergy of Panobinostat and Carfilzomib in Combination, Per Subject.
Subject MM-96
|
2.2 Combination index
|
|
Synergy of Panobinostat and Carfilzomib in Combination, Per Subject.
Subject MM-98
|
2.6 Combination index
|
|
Synergy of Panobinostat and Carfilzomib in Combination, Per Subject.
Subject MM-99
|
1.8 Combination index
|
|
Synergy of Panobinostat and Carfilzomib in Combination, Per Subject.
Subject MM-109
|
1.7 Combination index
|
|
Synergy of Panobinostat and Carfilzomib in Combination, Per Subject.
Subject MM-111
|
62.2 Combination index
|
PRIMARY outcome
Timeframe: At baselinePopulation: CI score was not reported for subject MM-82
Concentration of panobinostat and dexamethasone in combination leading to 90% growth inhibition of multiple myeloma cells in-vitro. The combination index (CI) is calculated using formula: CI = (\[D1\] in the combination / \[D1\] alone) + (\[D2\] in the combination / \[D2\] alone). Key: CI = 1 no synergy; CI\<1 synergy; CI\>1 antagonism.
Outcome measures
| Measure |
Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone
n=8 Participants
Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Synergy of Panobinostat and Dexamethasone in Combination, Per Subject
Subject MM-91
|
1.3 CI score
|
|
Synergy of Panobinostat and Dexamethasone in Combination, Per Subject
Subject MM-92
|
2.6 CI score
|
|
Synergy of Panobinostat and Dexamethasone in Combination, Per Subject
Subject MM-95
|
1.4 CI score
|
|
Synergy of Panobinostat and Dexamethasone in Combination, Per Subject
Subject MM-96
|
0.6 CI score
|
|
Synergy of Panobinostat and Dexamethasone in Combination, Per Subject
Subject MM-98
|
1.2 CI score
|
|
Synergy of Panobinostat and Dexamethasone in Combination, Per Subject
Subject MM-99
|
0.9 CI score
|
|
Synergy of Panobinostat and Dexamethasone in Combination, Per Subject
Subject MM-109
|
4.6 CI score
|
|
Synergy of Panobinostat and Dexamethasone in Combination, Per Subject
Subject MM-111
|
1.2 CI score
|
Adverse Events
Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone
Serious events: 3 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone
n=9 participants at risk
Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Cardiac disorders
Non-ST segment elevation myocardial infarction
|
11.1%
1/9 • Number of events 1 • Adverse events after any administration of the study drug through 30 days after the last administration of therapy will be recorded and followed until resolution.
Only non-hematologic toxicities ≥ grade 3 will be reported as adverse events. Hospitalizations or prolongation of hospitalizations for protocol-schedule procedures, blood product transfusions, or social reasons (i.e. awaiting transport home) will not be considered a SAE.
|
|
Injury, poisoning and procedural complications
Fracture, pathologic
|
11.1%
1/9 • Number of events 1 • Adverse events after any administration of the study drug through 30 days after the last administration of therapy will be recorded and followed until resolution.
Only non-hematologic toxicities ≥ grade 3 will be reported as adverse events. Hospitalizations or prolongation of hospitalizations for protocol-schedule procedures, blood product transfusions, or social reasons (i.e. awaiting transport home) will not be considered a SAE.
|
|
Injury, poisoning and procedural complications
Fracture, non-pathologic
|
11.1%
1/9 • Number of events 1 • Adverse events after any administration of the study drug through 30 days after the last administration of therapy will be recorded and followed until resolution.
Only non-hematologic toxicities ≥ grade 3 will be reported as adverse events. Hospitalizations or prolongation of hospitalizations for protocol-schedule procedures, blood product transfusions, or social reasons (i.e. awaiting transport home) will not be considered a SAE.
|
|
Injury, poisoning and procedural complications
Fall
|
11.1%
1/9 • Number of events 1 • Adverse events after any administration of the study drug through 30 days after the last administration of therapy will be recorded and followed until resolution.
Only non-hematologic toxicities ≥ grade 3 will be reported as adverse events. Hospitalizations or prolongation of hospitalizations for protocol-schedule procedures, blood product transfusions, or social reasons (i.e. awaiting transport home) will not be considered a SAE.
|
Other adverse events
| Measure |
Chemo Assay and Treatment With Panobinostat, Carfilzomib, and Dexamethasone
n=9 participants at risk
Patients undergo collection of blood and/or bone marrow samples for testing via in vitro chemosensitivity assay. Regardless of assay results, patients receive panobinostat PO on days 1, 3, 5, 15, 17, and 19, and carfilzomib IV and dexamethasone PO on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity.
|
|---|---|
|
Vascular disorders
Hypertension
|
22.2%
2/9 • Number of events 2 • Adverse events after any administration of the study drug through 30 days after the last administration of therapy will be recorded and followed until resolution.
Only non-hematologic toxicities ≥ grade 3 will be reported as adverse events. Hospitalizations or prolongation of hospitalizations for protocol-schedule procedures, blood product transfusions, or social reasons (i.e. awaiting transport home) will not be considered a SAE.
|
|
Gastrointestinal disorders
Diarrhea
|
11.1%
1/9 • Number of events 1 • Adverse events after any administration of the study drug through 30 days after the last administration of therapy will be recorded and followed until resolution.
Only non-hematologic toxicities ≥ grade 3 will be reported as adverse events. Hospitalizations or prolongation of hospitalizations for protocol-schedule procedures, blood product transfusions, or social reasons (i.e. awaiting transport home) will not be considered a SAE.
|
|
Nervous system disorders
Syncope
|
11.1%
1/9 • Number of events 1 • Adverse events after any administration of the study drug through 30 days after the last administration of therapy will be recorded and followed until resolution.
Only non-hematologic toxicities ≥ grade 3 will be reported as adverse events. Hospitalizations or prolongation of hospitalizations for protocol-schedule procedures, blood product transfusions, or social reasons (i.e. awaiting transport home) will not be considered a SAE.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place