A Phase I/II, Multicenter, Open-label, Dose-escalation Study of Bendamustine in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Mayo Clinic
- Enrollment
- 70
- Locations
- 5
- Primary Endpoint
- Dose Limiting Toxicity of Bendamustine Hydrochloride and Lenalidomide in Combination With Dexamethasone (Phase I)
Study Overview
Brief Summary
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.
Detailed Description
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: bendamustine hydrochloride (Drug)
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.
Intervention: lenalidomide (Drug)
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.
Intervention: dexamethasone (Drug)
Outcomes
Primary Outcomes
Dose Limiting Toxicity of Bendamustine Hydrochloride and Lenalidomide in Combination With Dexamethasone (Phase I)
Time Frame: One cycle of treatment
The Maximum Tolerated Dose (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
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.
Secondary Outcomes
- Duration of Response (DOR) (Phase II)(Up to 2 years from study completion)
- Event Free Survival (Phase II)(Up to 2 years from study completion)
- Progression Free Survival (Phase II)(Up to 2 years from study completion)
- Overall Survival (Phase II)(at 6 months)