Bendamustine Hydrochloride, Lenalidomide, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma
- Conditions
- Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT01049945
- Lead Sponsor
- Mayo Clinic
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 70
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Arm I bendamustine hydrochloride 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. Arm I dexamethasone 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. Arm I lenalidomide 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.
- Primary Outcome Measures
Name Time Method Dose Limiting Toxicity of Bendamustine Hydrochloride and Lenalidomide in Combination With Dexamethasone (Phase I) 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). 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 Outcome Measures
Name Time Method Duration of Response (DOR) (Phase II) Up to 2 years from study completion DOR is the time from the date the patient's objective status is first noted to be PR or better to the earliest date of progression (PD=Increase of \> 25% from lowest response value in Serum/Urine M-component) is documented. Treatment response was assessed using the International Myeloma Working Group uniform criteria. 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.
Event Free Survival (Phase II) Up to 2 years from study completion The event-free survival time is defined as the time from registration to disease progression (PD=Increase of \> 25% from lowest response value in Serum/Urine M-component) while receiving bendamustine, lenalidomide, and dexamethasone, death due to any cause, or subsequent treatment for multiple myeloma. The distribution of event-free survival will be estimated using the method of Kaplan-Meier. Treatment response was assessed using the International Myeloma Working Group uniform criteria.
Progression Free Survival (Phase II) Up to 2 years from study completion The progression-free survival time is defined as the time from registration to disease progression (PD=Increase of \> 25% from lowest response value in Serum/Urine M-component) while receiving bendamustine, lenalidomide, and dexamethasone or death due to any cause, whichever comes first. The distribution of progression-free survival will be estimated using the method of Kaplan-Meier. Treatment response was assessed using the International Myeloma Working Group uniform criteria.
Overall Survival (Phase II) at 6 months The overall survival time is defined as the time from registration to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier. The overall survival rate at 6 months is defined as the percentage of participants who are alive at 6 months.
Trial Locations
- Locations (5)
City of Hope
🇺🇸Duarte, California, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
Washington Universtiy School of Medicine
🇺🇸Saint Louis, Missouri, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States