Bendamustine + Pomalidomide + Dex in R/R Multiple Myeloma
This study is designed as a phase I-II, open label, dose finding study.
Study treatment will be as follows, in 28 day cycles:
- Pomalidomide: once daily orally (PO) dosing on days 1-21, every 28 days
- Bendamustine: once intravenously (IV) dosing on day 1, every 28 days
- Dexamethasone: weekly PO or IV dosing on days 1, 8, 15, and 22.
After completing 6 cycles of treatment, dexamethasone may be decreased to 20mg per investigator discretion. After completing 12 cycles of treatment, patients will proceed to the maintenance phase of the study. Patients will receive Pomalidomide on day 1-21, every 28 days and dexamethasone on days 1, 8, 15, and 22 every 28 days until time of progression.
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I-II Study of the Combination of Bendamustine and Pomalidomide With Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma|
- Maximum tolerated dose level [ Time Frame: one year ] [ Designated as safety issue: Yes ]In the phase I dose escalation portion, patients will be sequentially enrolled in 4 cohorts at dose levels defined in section 3.1 in a standard 3+3 design until the maximum tolerated dose (MTD) is reached. If dose limiting toxicity (DLT) is observed in 2 or more of the six patients at the same dosing level while DLT is observed in only 1 or none of the 6 patients at the dosing level immediately below it, then the lower dosing level will be defined as the maximum tolerated dose (MTD). Up to 24 patients will be enrolled in phase I portion.
- Response Rate [ Time Frame: 2 cycles (approximately 2 months) ] [ Designated as safety issue: No ]
The number of patients achieving a complete response (CR) or partial response (PR). Response is defined by the International Myeloma Working Group as:
CR- Negative immunofixation on serum and urine and disappearance of soft tissue plasmacytomas and < 5% plasma cells in bone marrow
PR- > 50% reduction of serum M-protein and urine M-protein by >90% or to < 200 mg/24 h OR > 50% decrease in the difference between involved and uninvolved free light chain levels OR > 50% reduction in plasma cells if baseline levels > 30% and a > 50% reduction in the size of soft tissue plasmacytomas if present at baseline
- Overall response rate [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]
The number of patients achieving stable disease (SD), partial response (PR), very good partial response (VGPR), complete response (CR) or stringent complete response (sCR)
sCR = CR as defined in Primary Outcome measure 2 plus normal free light chain ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence
VGPR = Serum and urine M-protein detectable by immunofixation but not on electrophoresis or > 90% reduction in serum M-protein plus urine M-protein level < 100 mg/24 h
SD = Not meeting criteria for CR, VGPR, PR, or progressive disease
- Time to progression [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]Time to progression - defined as time elapsed in patients between achievement of response and disease progression
- Time to next therapy [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]Time to next Therapy - defined as the time elapsed for patients from initiation of study therapy until initiation of next therapy
- Progression free survival [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]The time elapsed for patients between initiation of study therapy and either disease progression or death
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||January 2023|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
After 6 cycles of treatment, dexamethasone may be decreased to 20mg. After total 12 cycles of treatment, subjects will proceed to the maintenance phase until time of progression:
Study treatment will be administered starting at Cohort 1 for up to four sequential cohorts, with 3-6 patients in each cohort. Once the maximum tolerated dose (MTD) is reached, any additional patients will be enrolled at the MTD level.
Bendamustine will be administered intravenously over 10 minutes on day 1, every 28 days for 12 cycles.
Other Name: TreandaDrug: Pomalidomide
Pomalidomide will be administered once daily orally (PO) on days 1-21, every 28 days until disease progression or death.
Other Names:Drug: Dexamethasone
Dexamethasone will be administered weekly orally or intravenously on days 1, 8, 15, and 22 every 28 days until disease progression or death. After 6 cycles of treatment, the dose may be reduced to 20mg at investigator's discretion. For subjects ≥ 75 years of age, the starting dose of dexamethasone is 20 mg/day on Days 1, 8, 15 and 22 of each 28-day treatment cycle.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01754402
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Cristina Gasparetto, MD||Duke University|