Bendamustine Hydrochloride, Lenalidomide, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma
This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
First received: January 14, 2010
Last updated: March 23, 2015
Last verified: March 2015
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
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||A Phase I/II, Multicenter, Open-label, Dose-escalation Study of Bendamustine in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma
Primary Outcome Measures:
- 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.
Secondary Outcome Measures:
- 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:
| 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
- bendamustin hydrochloride
- cytostasan hydrochloride
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.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Diagnosis of MM and documentation of at least 1 prior therapy (induction therapy followed by stem cell transplantation is considered one prior therapy) but not more than two previous therapies
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide
- Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
- Able to take aspirin (325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA or at high risk of developing thrombosis may use warfarin or low molecular weight heparin)
- AST (SGOT) and ALT (SGPT) =< 3.0 x upper limit of normal (ULN)
- Creatinine clearance >= 60 mL/min (Cockcroft-Gault calculation) for patients enrolled in Phase 1 and Creatinine clearance >= 30 mL/min (Cockcroft-Gault calculation) for patients enrolled in phase 2 portion
- Patients with measurable disease, defined by any of the following: serum monoclonal protein >= 1.0 g by protein electrophoresis; > 200 mg of monoclonal protein in the urine on 24-hour electrophoresis; serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum immunoglobulin kappa to lambda free light chain ratio; or monoclonal bone marrow plasmacytosis >= 30% (evaluable disease)
- All necessary baseline studies for determining eligibility must be obtained within 21 days prior to enrollment
- Subject has an ECOG =< 2 OR Karnofsky >= 60% performance status; patients with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible
- FCBP must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing
- Absolute neutrophil count (ANC) >= 1,000 cells/dL (1.0 x 10^9/L) (growth factors cannot be used within 14 days of first drug administration)
- Untransfused platelet count >= 75,000 cells/dL (50 x 10^9/L) for patients in whom < 50% of bone marrow nucleated cells are plasma cells; but platelet count >=50,000/dL for patients in whom 50% of bone marrow nucleated cells are plasma cells
- Total Bilirubin =< 1.5 mg/dL
- Hemoglobin >= 8.0 g/dl
- Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
- Patients may be receiving concomitant therapy with bisphosphonates and low dose corticosteroids (e.g., prednisone up to but no more than 10 mg p.o. q.d. or its equivalent) for symptom management and comorbid conditions; doses of corticosteroid should be stable for at least 7 days prior to study treatment
- Prior radiation therapy within 2 weeks of the first dose of study treatment
- Known active infection requiring parenteral or oral anti-infective treatment
- Serious psychiatric illness, active alcoholism, or drug addiction that may hinder or confuse follow-up evaluation
- Patient has hypersensitivity to any of the components of study therapy - Known HIV or active hepatitis B or C viral infection
- Known hypersensitivity to required prophylactic medications
- Patient has received other investigational drugs within 14 days before enrollment
- Pregnant or breast-feeding females (lactating females must agree not to breast feed while taking lenalidomide)
- Subjects with evidence of mucosal or internal bleeding and/or platelet transfusion refractory (i.e., unable to maintain a platelet count >= 50,000 cells/mm^3)
- Concurrent therapy with a marketed or investigational anticancer therapy
- Any medical conditions that, in the Investigator's opinion, would impose excessive risk to the patient
- Other investigational agents are not to be used during the study
- Prior peripheral stem cell transplant within 12 weeks of the first dose of study treatment
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01049945
|City of Hope
|Duarte, California, United States, 91010 |
|Mayo Clinic in Florida
|Jacksonville, Florida, United States, 55904 |
|University of Chicago
|Chicago, Illinois, United States, 60637-1470 |
|Rochester, Minnesota, United States, 55905 |
|Washington Universtiy School of Medicine
|St. Louis, Missouri, United States, 63110 |
||Shaji K. Kumar, M.D.
||Vivek Roy, M.D.
||Mayo Clinic in Florida
No publications provided
History of Changes
|Other Study ID Numbers:
|Study First Received:
||January 14, 2010
|Results First Received:
||March 23, 2015
||March 23, 2015
||United States: Food and Drug Administration
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on February 04, 2016
Neoplasms, Plasma Cell
Blood Protein Disorders
Immune System Diseases
Neoplasms by Histologic Type
Nitrogen Mustard Compounds
Angiogenesis Modulating Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal