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

NCT00920855 | Completed Phase 1 Results

• 1 other identifier: C18083/1063/MM/US
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 13

Brief Summary

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).

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 1 - 28

Secondary Outcomes (8)

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

  Up to 7.5 months (eight 28-day cycles)

• Participants' Best Tumor Response as Assessed by the Investigator

  up to 7.5 months (eight 28-day cycles)

• Kaplan-Meier Estimate for Time to Progression (TTP)

  up to 8.6 months

• Kaplan-Meier Estimate for Progression-Free Survival

  up to 23 months

• Time to the First Response

  up to 8.5 months

Study Arms (1)

Bendamustine and Bortezomib

EXPERIMENTAL

Bendamustine in escalating doses of 50, 70 or 90 mg/m\^2 as combination therapy with bortezomib at 1.0 mg/m\^2/dose administered for up to eight 28 day cycles.

Drug: bendamustine; Drug: bortezomib

Interventions

bendamustine DRUG

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.

Also known as: CEP-18083, Bendamustine hydrochloride, TREANDA

Bendamustine and Bortezomib

bortezomib DRUG

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.

Also known as: VELCADE®

Bendamustine and Bortezomib

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cephalon: lead

Study Sites (13)

Pacific Oncololgy & Hematology

Encinitas, California, United States

Location

Capitol Hematology Oncology

Roseville, California, United States

Location

University Of California, San Diego

San Diego, California, United States

Location

James R. Berenson, M.D., Inc.

West Hollywood, California, United States

Location

George Washington University

Washington D.C., District of Columbia, United States

Location

Northshore University Health System

Evanston, Illinois, United States

Location

Alivin & Lois Lapidus Cancer Institute

Baltimore, Maryland, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

Location

Sophia Gordon Cancer Center at Lahey Clinic

Burlington, Massachusetts, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, United States

Location

Charleston Hematology Oncology, PA

Charleston, South Carolina, United States

Location

Family Cancer Center, PLLC

Collierville, Tennessee, United States

Location

Fairfax Northern Virginia Hematology Oncology

Fairfax, Virginia, United States

Location

Related Publications (1)

• Berenson JR, Yellin O, Bessudo A, et al. Bendamustine combined with bortezomib has efficacy in patients with relapsed or refractory multiple myeloma: a phase 1/2 study. Blood (ASH Annual Meeting Abstracts). 2011;118 (suppl 21):abstract 1857

  RESULT

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bendamustine Hydrochloride; Bortezomib

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; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.

ustevatrials@tevapharm.com

215-591-3000

Study Officials

• Sponsor's Medical Expert

  Cephalon

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: June 11, 2009
• First Posted: June 15, 2009
• Study Start: June 1, 2009
• Primary Completion: July 1, 2011
• Study Completion: December 1, 2011
• Last Updated: October 4, 2012
• Results First Posted: September 17, 2012

Record last verified: 2012-09

Locations

US (13)