Study of Bendamustine Combined With Bortezomib for Patients With Relapsed/Refractory Multiple Myeloma

Phase 2CompletedNCT00920855

Cephalon40 enrolled

Overview

The primary objective of this study is to assess the safety and tolerability of bendamustine as combination therapy with bortezomib for patients with relapsed/refractory multiple myeloma (MM).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Multiple Myeloma

Interventions

bendamustineDRUG

Bendamustine was administered to 3 cohorts of patients at escalating doses of 50 (cohort 1), 70 (cohort 2) and 90 mg/m\^2/dose (cohort 3). Doses were administered by intravenous (iv) infusion once daily on days 1 and 4 of each 28-day cycle. Each iv was administered over 60 minutes and followed the injection of bortezomib. Bortezomib will be administered to patients at a dose of 1.0 mg/m2/dose as an iv push over 3 to 5 seconds followed by a standard saline flush or through a running iv line. Doses are to be administered to patients on days 1, 4, 8 and 11 of the 28-day cycle.

bortezomibDRUG

Bortezomib was administered at a dose of 1.0 mg/m\^2/dose as an intravenous (iv) push over 3 to 5 seconds followed by a standard saline flush or through a running iv line. Doses are to be administered on days 1, 4, 8 and 11 of each 28-day cycle.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: The patient: * has a diagnosis of multiple myeloma. * currently has multiple myeloma with measurable disease. * must have received at least 1 previous treatment regimen and shows signs of progressive disease at the time of study entry. * if a woman of child bearing potential (not surgically sterile or at least 12 months naturally postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study. * if a man, must agree to use an acceptable method of contraception throughout the study and for 90 days after last dose study drug. * must have an Eastern Cooperative Oncology Group (ECOG) performance status not greater than 2. * must have a life-expectancy of greater than 3 months. * must meet specific protocol-related hematological and laboratory criteria within 14 days of enrollment. Exclusion Criteria: The patient has: * had a prior malignancy within the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix). * plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein) and skin changes (POEMS) syndrome. * plasma cell leukemia. * non-measurable multiple myeloma. * Common Terminology Criteria for Adverse Events (CTCAE) grade 2 (or greater) peripheral neuropathy within 14 days before enrollment. * previously participated in a Cephalon-sponsored clinical study with bendamustine. * impaired cardiac function or clinically significant cardiac diseases. * undergone major surgery within 4 weeks prior to screening or has not recovered from side effects of such therapy. * severe hypercalcemia. * other concurrent severe and/or uncontrolled medical or psychiatric conditions. * known positivity for human immunodeficiency virus (HIV) or hepatitis B or C. * a history of allergic reaction attributable to compounds of similar chemical or biological composition to bendamustine, bortezomib, boron, or mannitol. * received chemotherapy within 3 weeks before enrollment, with the exception of nitrosoureas, which should be discontinued at least 6 weeks before enrollment. * received corticosteroids (greater than 10 mg/day prednisone or equivalent) within 3 weeks before enrollment. * received immunotherapy, antibody, or radiation therapy within 4 weeks before enrollment. * a status as a pregnant or lactating woman. Any women becoming pregnant during the study will be withdrawn from the study. * a status as a male whose sexual partner is a woman of childbearing potential not using effective birth control. * used an investigational drug within 1 month before the screening visit.

Locations (13)

Pacific Oncololgy & Hematology

Encinitas, California, United States

Capitol Hematology Oncology

Roseville, California, United States

University Of California, San Diego

San Diego, California, United States

Outcomes

Primary Outcomes

Participants With Dose Limiting Toxicity (DLT)

Maximum tolerated dose was the dose that was 1 step lower than the dose where at least one third of patients experienced DLT. A DLT was defined as any of the following occurring during the first cycle: * grade 4 hematologic toxicity without regard for relationship to study drug treatment * thrombocytopenia grade 3 with grade 3 or grade 4 hemorrhage * grade 3 febrile neutropenia * grade 3 or grade 4 nausea and vomiting refractory to anti emetic therapy * any study drug related grade 3 or grade 4 nonhematologic toxicity * any drug related death Toxicity grades (3=severe AE and 4=life-threatening or disabling AE) were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.

Time frame: Day 1 - 28

Secondary Outcomes

Percentage of Participants With An Overall Tumor Response As Assessed By the Investigator

Overall tumor response is the sum of a complete response (CR), very good partial response (VGPR), partial response (PR) and minimal response (MR). A modified version of the Bladé criteria for response was used. Abbreviated definitions for the response categories can be found in the description of outcome #3.

Time frame: Up to 7.5 months (eight 28-day cycles)

Participants' Best Tumor Response as Assessed by the Investigator

Abbreviated criteria for response categories: CR includes the disappearance of the original monoclonal protein (M-protein) from blood and urine, and \<5% plasma cells in the bone marrow, and no increase in size/number of lytic bone lesions, and disappearance of soft tissue plasmacytomas for \>=4 weeks. VGPR includes serum and urine M-protein detectable by immunofixation but not electrophoresis, and reduction in 24-hr urinary light chain excretion by \<100 mg, and disappearance of soft tissue plasmacytomas for \>= 4 weeks, and no increase in size/number of lytic bone lesions. PR includes a \>=50% reduction in serum M-protein, and reduction in 24-hr urinary light chain excretion by either \>=90% or to \<200 mg, and \>=50% reduction in size of soft tissue plasmacytomas, and no increase in size/number of lytic bone lesions. MR includes a \>=25% and \<=49% reduction in serum M-protein. SD does not meet criteria for the other response categories. See outcome #4 for a definition of PD.

Data from ClinicalTrials.gov

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