Bendamustine Hydrochloride, Lenalidomide, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma
RATIONALE: Drugs used in chemotherapy, such as bendamustine hydrochloride and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Lenalidomide may stimulate the immune system in different ways and stop cancer cells from growing. Giving bendamustine hydrochloride together with lenalidomide and dexamethasone may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of bendamustine hydrochloride and lenalidomide when given together with dexamethasone and to see how well they work in treating patients with relapsed multiple myeloma.
Refractory Multiple Myeloma
Drug: bendamustine hydrochloride
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II, Multicenter, Open-label, Dose-escalation Study of Bendamustine in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma|
- Maximum Tolerated Dose of Bendamustine Hydrochloride and Lenalidomide in Combination With Dexamethasone (Phase I) [ Time Frame: One cycle of treatment ] [ Designated as safety issue: Yes ]
The MTD is the dose level below that at which a dose limiting toxicity (DLT) is observed in ≥ 33% (i.e., ≥ 2 of 6) subjects in a cohort. A dose limiting toxicity is defined as one of the following adverse events in the Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 deemed at least possibly related to treatment:
- Grade 2 neuropathy with pain
- Any grade 3 Non-Hematologic toxicity
- Any grade Non-Hematologic event requiring a dose reduction in cycle 1 or delaying the next cycle by >14 days.
- Grade 4 neutropenia
- Febrile neutropenia
- Grade 4 thrombocytopenia
- Grade 3 thrombocytopenia associated with bleeding
- Any Hematologic event requiring a dose reduction in cycle 1 or a delay in the next cycle of treatment by >14 days.
We are reporting the results of this endpoint as the number of DLTs per dose level.
- Confirmed Response Rate (Dose Level 4) Reported as the Percentage of Patients Achieving a Confirmed Response (sCR, CR, VGPR, or PR). [ Time Frame: Up to 6 cycles of treatment ] [ Designated as safety issue: No ]
Complete response (CR)
- Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow.
Stringent complete response (sCR) - A CR plus normal FLC ratio and no clonal cells in bone marrow
Near complete response (nCR) A CR, with the persistence of original monoclonal protein
Very good partial response (VGPR)
- Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-component plus urine M-component <100 mg per 24 h
Partial response (PR)
- ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg per 24 h.
- a ≥50% decrease in the difference between involved and uninvolved FLC levels
- or a ≥50% reduction in plasma cells is required in place of M-protein, if ≥30% at baseline.
- Duration of Response (Phase II) [ Time Frame: Up to 2 years from study completion (6 years total) ] [ Designated as safety issue: No ]
- Time to Progression (Phase II) [ Time Frame: Up to 2 years from study completion (6 years total) ] [ Designated as safety issue: No ]
- Progression Free Survival (Phase II) [ Time Frame: Up to 2 years from study completion (6 years total) ] [ Designated as safety issue: No ]
- Overall Survival (Phase II) [ Time Frame: Up to 2 years from study completion (6 years total) ] [ Designated as safety issue: No ]
|Study Start Date:||February 2010|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Patients receive dexamethasone orally or IV on days 1, 8, 15, and 22; bendamustine hydrochloride IV over 30 minutes on days 1 and 2; and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: bendamustine hydrochloride
Other Names:Drug: lenalidomide
Other Names:Drug: dexamethasone
Given orally or IV
PRIMARY OBJECTIVES: I. To determine the Maximum Tolerated Dose (MTD) of bendamustine and lenalidomide in combination with dexamethasone in subjects with Multiple Myeloma (MM) in first or second relapse. (Phase I) II. To evaluate the confirmed response rate of bendamustine in combination with lenalidomide and dexamethasone in subjects with MM in first or second relapse. (Phase II) SECONDARY OBJECTIVES: I. To evaluate the safety of bendamustine in combination with lenalidomide and dexamethasone. (Phase I and II) II. To evaluate time-to-tumor-progression, progression-free survival, duration of response, and overall survival. (Phase II) OUTLINE: This is a phase I dose escalation study of bendamustine hydrochloride and lenalidomide followed by a phase II study. Patients receive dexamethasone orally or IV on days 1, 8, 15, and 22; bendamustine hydrochloride IV over 30 minutes on days 1 and 2; and oral lenalidomide once daily on days 1-21. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients achieving at least stable disease after 6 courses may continue to receive lenalidomide and dexamethasone as above in the absence of disease progression or unacceptable toxicity. Dexamethasone may be discontinued after 12 courses of therapy at the treating investigator's discretion. After completion of study treatment, patients are followed at 4 weeks and then periodically for up to 2 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01049945
|United States, California|
|City of Hope|
|Duarte, California, United States, 91010|
|United States, Florida|
|Mayo Clinic in Florida|
|Jacksonville, Florida, United States, 55904|
|United States, Illinois|
|University of Chicago|
|Chicago, Illinois, United States, 60637-1470|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, Missouri|
|Washington Universtiy School of Medicine|
|St. Louis, Missouri, United States, 63110|
|Study Chair:||Shaji K. Kumar, M.D.||Mayo Clinic|
|Principal Investigator:||Vivek Roy, M.D.||Mayo Clinic in Florida|