Bendamustine Hydrochloride, Lenalidomide, and Dexamethasone in Treating Patients With Relapsed Multiple Myeloma

NCT01049945 | Completed Phase 1 Results DMC

• 4 other identifiers: MMRC-020-021NCI-2009-0153509-004211C18083/6125
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 5

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.

Conditions

Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Dose Limiting Toxicity of Bendamustine Hydrochloride and Lenalidomide in Combination With Dexamethasone (Phase I)

  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.

  One cycle of treatment

• Confirmed Response Rate (Dose Level 4) Reported as the Percentage of Patients Achieving a Confirmed Response (sCR, CR, VGPR, or PR).

  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.

  Up to 6 cycles of treatment

Secondary Outcomes (4)

• 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

Study Arms (1)

Arm I

EXPERIMENTAL

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; Drug: lenalidomide; Drug: dexamethasone

Interventions

bendamustine hydrochloride DRUG

Given IV

Also known as: bendamustin hydrochloride, bendamustine, cytostasan hydrochloride, Ribomustin, SDX-105, Treanda

Arm I

lenalidomide DRUG

Given orally

Also known as: CC-5013, IMiD-1, Revlimid

Arm I

dexamethasone DRUG

Given orally or IV

Also known as: Aeroseb-Dex, Decaderm, Decadron, Decaspray, DM, DXM

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (5)

City of Hope

Duarte, California, 91010, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 55904, United States

Location

University of Chicago

Chicago, Illinois, 60637-1470, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington Universtiy School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Kumar SK, Krishnan A, LaPlant B, Laumann K, Roy V, Zimmerman T, Gertz MA, Buadi FK, Stockerl Goldstein K, Birgin A, Fiala M, Duarte L, Maharaj M, Levy J, Vij R. Bendamustine, lenalidomide, and dexamethasone (BRD) is highly effective with durable responses in relapsed multiple myeloma. Am J Hematol. 2015 Dec;90(12):1106-10. doi: 10.1002/ajh.24181. Epub 2015 Oct 6.

  PMID: 26331432 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bendamustine Hydrochloride; Lenalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Isoindoles; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Shaji K. Kumar, M.D.
• Organization: Mayo Clinic

kumar.shaji@mayo.edu

Study Officials

• Shaji K. Kumar, M.D.

  Mayo Clinic

  STUDY CHAIR

• Vivek Roy, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2010
• First Posted: January 15, 2010
• Study Start: February 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: September 16, 2015
• Last Updated: February 11, 2020
• Results First Posted: March 30, 2015

Record last verified: 2016-04

Locations

US (5)