Trial Outcomes & Findings for Carfilzomib + High Dose Melphalan as Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation (NCT NCT01690143)
NCT ID: NCT01690143
Last Updated: 2018-08-07
Results Overview
The maximum tolerated dose of carfilzomib that can be safely combined with high dose melphalan as conditioning regimen prior to autologous hematopoietic cell transplantation in patients with relapsed multiple myeloma meeting eligibility criteria.
COMPLETED
PHASE1/PHASE2
45 participants
Up to 4 1/2 months
2018-08-07
Participant Flow
Participant milestones
| Measure |
Carfilzomib + High Dose Melphalan
Single arm.
Carfilzomib: Subjects will receive the appropriate dose of carfilzomib (according to assigned cohort in phase 1 and at the determined MTD in phase 2) on days -3 and -2. Carfilzomib will be infused over 30 minutes. Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.
Melphalan: Subjects will receive 200 mg/m2 of intravenous melphalan on Day -2. Administered as an intravenous push or a fast infusion according to institutional standard operating procedure (SOP). Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.
|
|---|---|
|
Overall Study
STARTED
|
45
|
|
Overall Study
COMPLETED
|
44
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Carfilzomib + High Dose Melphalan
Single arm.
Carfilzomib: Subjects will receive the appropriate dose of carfilzomib (according to assigned cohort in phase 1 and at the determined MTD in phase 2) on days -3 and -2. Carfilzomib will be infused over 30 minutes. Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.
Melphalan: Subjects will receive 200 mg/m2 of intravenous melphalan on Day -2. Administered as an intravenous push or a fast infusion according to institutional standard operating procedure (SOP). Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Carfilzomib + High Dose Melphalan as Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation
Baseline characteristics by cohort
| Measure |
Carfilzomib + High Dose Melphalan
n=45 Participants
Single arm.
Carfilzomib: Subjects will receive the appropriate dose of carfilzomib (according to assigned cohort in phase 1 and at the determined MTD in phase 2) on days -3 and -2. Carfilzomib will be infused over 30 minutes. Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.
Melphalan: Subjects will receive 200 mg/m2 of intravenous melphalan on Day -2. Administered as an intravenous push or a fast infusion according to institutional standard operating procedure (SOP). Prophylaxis of chemotherapy induced nausea and vomiting will follow institutional guidelines and SOPs.
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|---|---|
|
Age, Continuous
|
58 years
n=99 Participants
|
|
Sex: Female, Male
Female
|
25 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
20 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Non-Hispanic Whites
|
26 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Non-Hispanic Blacks
|
18 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Other
|
1 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Up to 4 1/2 monthsPopulation: Patients who underwent transplantation during phase 1
The maximum tolerated dose of carfilzomib that can be safely combined with high dose melphalan as conditioning regimen prior to autologous hematopoietic cell transplantation in patients with relapsed multiple myeloma meeting eligibility criteria.
Outcome measures
| Measure |
Patients Undergoing Transplantation
n=15 Participants
All patients who receive transplant in the phase 1 of the study
|
|---|---|
|
Maximum Tolerated Dose (MTD) of Carfilzomib Plus Melphalan as Conditioning for Autologous Hematopoietic Cell Transplantation in Patients With Relapsed Multiple Myeloma(MM) [Phase I Portion of Study]
|
56 mg/m2
|
PRIMARY outcome
Timeframe: Up to 17 monthsPopulation: All patients who underwent transplantation
VGPR defined as any one of the following: ≥ 90% reduction of serum M-protein; ≥ 90% reduction in 24-hour urinary M-protein or decrease to \< 100 mg per 24 hour; ≥ 50% decrease in the difference between involved and uninvolved FLC levels or a 50% decrease in level of involved FLC with 50% decrease in ratio; ≥ 50% reduction in bone marrow plasma cells; ≥ 50% reduction in the size of soft tissue plasmacytomas.
Outcome measures
| Measure |
Patients Undergoing Transplantation
n=44 Participants
All patients who receive transplant in the phase 1 of the study
|
|---|---|
|
Very Good Partial Response (VGPR) Rate.
|
26 Participants
|
PRIMARY outcome
Timeframe: Up to 17 monthsCR defined as the following: Negative immunofixation of the serum and urine. If only the measurable non-bone marrow parameter was free light chain, normalization of free light chain ratio. \< 5% plasma cells in bone marrow. And, disappearance of any soft tissue plasmacytomas.
Outcome measures
| Measure |
Patients Undergoing Transplantation
n=44 Participants
All patients who receive transplant in the phase 1 of the study
|
|---|---|
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Complete Response (CR) Rate.
|
10 Participants
|
PRIMARY outcome
Timeframe: Up to 1 month.Population: All patients
Neutrophil engraftment is defined as the first of three consecutive days with absolute neutrophil count \>500/mm3. Platelet engraftment is defined as the first of 3 consecutive days of platelets \> 20,000/mm3 without platelet transfusion in the prior 7 days.
Outcome measures
| Measure |
Patients Undergoing Transplantation
n=44 Participants
All patients who receive transplant in the phase 1 of the study
|
|---|---|
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Median Time for Neutrophil and Platelet Engraftment.
|
10 days
Interval 8.0 to 16.0
|
PRIMARY outcome
Timeframe: Up to 4 1/2 monthsGrading of AE's is performed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Outcome measures
| Measure |
Patients Undergoing Transplantation
n=44 Participants
All patients who receive transplant in the phase 1 of the study
|
|---|---|
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Frequency of Grades 3 and 4 Non-hematologic Adverse Events During the Transplant Component ( 135 Days)
|
22 Participants
|
Adverse Events
Patients Undergoing Transplantation
Serious adverse events
| Measure |
Patients Undergoing Transplantation
n=44 participants at risk
All patients who receive transplant in the phase 1+2 of the study
|
|---|---|
|
Cardiac disorders
heart failure
|
2.3%
1/44 • Number of events 1 • 12 months
|
|
Renal and urinary disorders
renal failure
|
2.3%
1/44 • Number of events 1 • 12 months
|
Other adverse events
| Measure |
Patients Undergoing Transplantation
n=44 participants at risk
All patients who receive transplant in the phase 1+2 of the study
|
|---|---|
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Infections and infestations
Infection
|
38.6%
17/44 • Number of events 17 • 12 months
|
|
Gastrointestinal disorders
diarrhea
|
11.4%
5/44 • Number of events 5 • 12 months
|
|
Cardiac disorders
hypertension
|
9.1%
4/44 • Number of events 4 • 12 months
|
|
Immune system disorders
rash
|
6.8%
3/44 • Number of events 3 • 12 months
|
|
Endocrine disorders
hyperkalemia
|
6.8%
3/44 • Number of events 3 • 12 months
|
Additional Information
Luciano J Costa, Principal Investigator
University of Alabama at Birmingham
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place