Trial Outcomes & Findings for High-Dose Weekly Carfilzomib Plus Cyclophosphamide and Dexamethasone in the Treatment of Relapsed Multiple Myeloma (NCT NCT02597062)
NCT ID: NCT02597062
Last Updated: 2023-08-28
Results Overview
Response rate to protocol treatment after 4 cycles is define by stringent complete response, complete response, partial response, very good partial response, minimal response. Complete response: Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow biopsy Stringent complete response: Complete response plus Absence of clonal cells in bone marrow d by immunohistochemistry or immunofluorescence Very good partial response: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein with urine M-protein level \<100 mg/24 hours. Partial response: ≥50% reduction in serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 hours Minimal response: 25-49% reduction in serum M-protein, and 50-89% reduction in 24-hour urinary M-protein, if ≥ 200 mg/24 hours at baseline
COMPLETED
PHASE2
76 participants
4 months
2023-08-28
Participant Flow
Participant milestones
| Measure |
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone
20 mg/m2 day 1 of first cycle then escalated to 70 mg/m2 for all subsequent doses) given on days 1, 8, and 15 of a 28 day cycle plus weekly oral dexamethasone (\< 70 years, 40 mg; ≥ 70 years 20mg) and cyclophosphamide 300 mg/m2 capped at 500 mg
Carfilzomib
Cyclophosphamide
Dexamethasone
|
|---|---|
|
Overall Study
STARTED
|
76
|
|
Overall Study
COMPLETED
|
75
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone
20 mg/m2 day 1 of first cycle then escalated to 70 mg/m2 for all subsequent doses) given on days 1, 8, and 15 of a 28 day cycle plus weekly oral dexamethasone (\< 70 years, 40 mg; ≥ 70 years 20mg) and cyclophosphamide 300 mg/m2 capped at 500 mg
Carfilzomib
Cyclophosphamide
Dexamethasone
|
|---|---|
|
Overall Study
Ineligible
|
1
|
Baseline Characteristics
High-Dose Weekly Carfilzomib Plus Cyclophosphamide and Dexamethasone in the Treatment of Relapsed Multiple Myeloma
Baseline characteristics by cohort
| Measure |
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone
n=75 Participants
20 mg/m2 day 1 of first cycle then escalated to 70 mg/m2 for all subsequent doses) given on days 1, 8, and 15 of a 28 day cycle plus weekly oral dexamethasone (\< 70 years, 40 mg; ≥ 70 years 20mg) and cyclophosphamide 300 mg/m2 capped at 500 mg
Carfilzomib
Cyclophosphamide
Dexamethasone
|
|---|---|
|
Age, Continuous
|
66.0 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
27 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
48 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
3 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
1 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
|
2 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
68 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=99 Participants
|
|
Region of Enrollment
Canada
|
75 participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 4 monthsPopulation: All eligible patients how have received treatment.
Response rate to protocol treatment after 4 cycles is define by stringent complete response, complete response, partial response, very good partial response, minimal response. Complete response: Negative immunofixation on the serum and urine and Disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow biopsy Stringent complete response: Complete response plus Absence of clonal cells in bone marrow d by immunohistochemistry or immunofluorescence Very good partial response: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein with urine M-protein level \<100 mg/24 hours. Partial response: ≥50% reduction in serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to \<200 mg/24 hours Minimal response: 25-49% reduction in serum M-protein, and 50-89% reduction in 24-hour urinary M-protein, if ≥ 200 mg/24 hours at baseline
Outcome measures
| Measure |
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone
n=75 Participants
20 mg/m2 day 1 of first cycle then escalated to 70 mg/m2 for all subsequent doses) given on days 1, 8, and 15 of a 28 day cycle plus weekly oral dexamethasone (\< 70 years, 40 mg; ≥ 70 years 20mg) and cyclophosphamide 300 mg/m2 capped at 500 mg
Carfilzomib
Cyclophosphamide
Dexamethasone
|
|---|---|
|
Overall Response Rate After 4 Cycles
stringent complete response
|
4 Participants
|
|
Overall Response Rate After 4 Cycles
complete response
|
3 Participants
|
|
Overall Response Rate After 4 Cycles
very good partial response
|
32 Participants
|
|
Overall Response Rate After 4 Cycles
partial response
|
21 Participants
|
|
Overall Response Rate After 4 Cycles
minimal response
|
1 Participants
|
|
Overall Response Rate After 4 Cycles
no response
|
14 Participants
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: All treated patients were included in the analysis
Median time to progression or death assessed by biochemistry, radiology and immunology tests will be reported. Progression is evaluated in this study using the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) with any one or more of the following: 1. Increase of ≥ 25% from lowest response value in: Serum M-component and/or Urine M-component and/or Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels or Bone marrow plasma cell percentages. 2. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas 3. Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dL (0.115 g/L) or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
Outcome measures
| Measure |
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone
n=75 Participants
20 mg/m2 day 1 of first cycle then escalated to 70 mg/m2 for all subsequent doses) given on days 1, 8, and 15 of a 28 day cycle plus weekly oral dexamethasone (\< 70 years, 40 mg; ≥ 70 years 20mg) and cyclophosphamide 300 mg/m2 capped at 500 mg
Carfilzomib
Cyclophosphamide
Dexamethasone
|
|---|---|
|
Progression-free Survival
|
17.15 months
Interval 13.57 to 21.49
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: All treated patients
Median time to death in months will be reported
Outcome measures
| Measure |
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone
n=75 Participants
20 mg/m2 day 1 of first cycle then escalated to 70 mg/m2 for all subsequent doses) given on days 1, 8, and 15 of a 28 day cycle plus weekly oral dexamethasone (\< 70 years, 40 mg; ≥ 70 years 20mg) and cyclophosphamide 300 mg/m2 capped at 500 mg
Carfilzomib
Cyclophosphamide
Dexamethasone
|
|---|---|
|
Overall Survival
|
27.43 months
Interval 22.05 to 33.8
|
Adverse Events
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone
Serious adverse events
| Measure |
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone
n=75 participants at risk
20 mg/m2 day 1 of first cycle then escalated to 70 mg/m2 for all subsequent doses) given on days 1, 8, and 15 of a 28 day cycle plus weekly oral dexamethasone (\< 70 years, 40 mg; ≥ 70 years 20mg) and cyclophosphamide 300 mg/m2 capped at 500 mg
Carfilzomib
Cyclophosphamide
Dexamethasone
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
4.0%
3/75 • 3 years
|
|
Blood and lymphatic system disorders
Other blood and lymphatic system disorders
|
1.3%
1/75 • 3 years
|
|
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura
|
2.7%
2/75 • 3 years
|
|
Cardiac disorders
Heart failure
|
2.7%
2/75 • 3 years
|
|
Cardiac disorders
Mitral valve disease
|
1.3%
1/75 • 3 years
|
|
Cardiac disorders
Right ventricular dysfunction
|
1.3%
1/75 • 3 years
|
|
General disorders
Death NOS
|
1.3%
1/75 • 3 years
|
|
General disorders
Fatigue
|
1.3%
1/75 • 3 years
|
|
General disorders
Fever
|
5.3%
4/75 • 3 years
|
|
General disorders
Malaise
|
1.3%
1/75 • 3 years
|
|
General disorders
Non-cardiac chest pain
|
2.7%
2/75 • 3 years
|
|
Infections and infestations
Abdominal infection
|
1.3%
1/75 • 3 years
|
|
Infections and infestations
Device related infection
|
1.3%
1/75 • 3 years
|
|
Infections and infestations
Lung infection
|
18.7%
14/75 • 3 years
|
|
Infections and infestations
Other infections and infestations
|
1.3%
1/75 • 3 years
|
|
Infections and infestations
Sepsis
|
5.3%
4/75 • 3 years
|
|
Infections and infestations
Upper respiratory infection
|
4.0%
3/75 • 3 years
|
|
Injury, poisoning and procedural complications
Ankle fracture
|
1.3%
1/75 • 3 years
|
|
Injury, poisoning and procedural complications
Fracture
|
1.3%
1/75 • 3 years
|
|
Investigations
Alanine aminotransferase increased
|
4.0%
3/75 • 3 years
|
|
Investigations
Aspartate aminotransferase increased
|
4.0%
3/75 • 3 years
|
|
Investigations
Blood bilirubin increased
|
1.3%
1/75 • 3 years
|
|
Metabolism and nutrition disorders
Dehydration
|
1.3%
1/75 • 3 years
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
1.3%
1/75 • 3 years
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Other neoplasms benign, malignant and unspecified
|
1.3%
1/75 • 3 years
|
|
Nervous system disorders
Ischemia cerebrovascular
|
1.3%
1/75 • 3 years
|
|
Nervous system disorders
Other nervous system disorders
|
1.3%
1/75 • 3 years
|
|
Psychiatric disorders
Delirium
|
1.3%
1/75 • 3 years
|
|
Renal and urinary disorders
Acute kidney injury
|
1.3%
1/75 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome
|
1.3%
1/75 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
1.3%
1/75 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.3%
1/75 • 3 years
|
|
Vascular disorders
Other vascular disorders
|
1.3%
1/75 • 3 years
|
|
Vascular disorders
Thromboembolic event
|
2.7%
2/75 • 3 years
|
Other adverse events
| Measure |
Carfilzomib Plus Cyclophosphamide Plus Dexamethasone
n=75 participants at risk
20 mg/m2 day 1 of first cycle then escalated to 70 mg/m2 for all subsequent doses) given on days 1, 8, and 15 of a 28 day cycle plus weekly oral dexamethasone (\< 70 years, 40 mg; ≥ 70 years 20mg) and cyclophosphamide 300 mg/m2 capped at 500 mg
Carfilzomib
Cyclophosphamide
Dexamethasone
|
|---|---|
|
General disorders
Fatigue
|
16.0%
12/75 • 3 years
|
|
Infections and infestations
Lung infection
|
20.0%
15/75 • 3 years
|
|
Infections and infestations
Sepsis
|
6.7%
5/75 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
6.7%
5/75 • 3 years
|
|
Vascular disorders
Hypertension
|
9.3%
7/75 • 3 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place