Bendamustine Hydrochloride in Combination With Rituximab in Patients With Relapsed Refractory Mantle Cell Lymphoma

NCT00891839 | Completed Phase 2 Results

• 1 other identifier: C18083/2039/NL/US-CA
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 13

Brief Summary

The purpose of this study is to determine the efficacy and safety of the combination of bendamustine and rituximab in patients with relapsed/refractory mantle cell lymphoma.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (Complete Response + Partial Response) at the End of Cycles 3 and 6 Using the 2007 International Working Group Criteria

  The International Working Group (IWG) criteria (Cheson et al 2007) for a complete response is a complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. A partial response is at least a 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase should be observed in the size of other nodes, liver or spleen, and no new sites of disease should be observed. 95% CIs are calculated using binomial exact method.

  Month 3 (end of cycle 3), Month 6 (end of cycle 6)

Secondary Outcomes (5)

• Kaplan-Meier Estimate for Duration of Response

  Day 1 up to Month 43

• Kaplan-Meier Estimate for Progression-Free Survival

  Day 1 up to Month 45

• Kaplan-Meier Estimate for Overall Survival

  Day 1 up to Month 57

• Shifts in Baseline to Post-Treatment in Positron Emission Tomography (PET)

  Baseline (Days -30 to 0), post treatment (up to Month 9, 30 days following completion of therapy)

• Shifts in Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status

  Day 0 (baseline) up to Month 8

Study Arms (1)

Bendamustine+Rituximab

EXPERIMENTAL

Patients receive bendamustine at 90 mg/m\^2 intravenously (iv) on days 1 and 2, and 375 mg/m\^2 of rituximab by iv on day 1 of each 28-day cycle. Six 28-day cycles were planned and up to 8 cycles permitted for patients who do not have progressive disease and who have not achieved a complete response (CR).

Drug: Bendamustine; Drug: Rituximab

Interventions

Bendamustine DRUG

Bendamustine at 90 mg/m\^2 intravenously (iv) on days 1 and 2 of each 28-day cycle. Dosage calculations for bendamustine are based on the patient's body surface area (BSA) at baseline, using actual weight for calculations. If there is a 10% change in a patient's weight during treatment, the most recent weight is used to recalculate the BSA. The new BSA is used in determining the doses to be administered in any subsequent cycles.

Also known as: bendamustine HCl, TREANDA®, CEP-18083

Bendamustine+Rituximab

Rituximab DRUG

Patients receive 375 mg/m\^2 of rituximab, administered by iv infusion on day 1 of every 28-day cycle of treatment. Dosage calculations for rituximab are based on the patient's BSA at baseline, using actual weight for calculations. If there is a 10% change in a patient's weight during treatment, the most recent weight is used to recalculate the BSA. The new BSA is used in determining the doses to be administered in any subsequent cycles.

Also known as: Rituxan

Bendamustine+Rituximab

Eligibility Criteria

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

You may qualify if:

• histopathologically confirmed diagnosis of typical or atypical mantle cell lymphoma, except for blastoid type.
• documented relapsed/refractory mantle cell lymphoma.
• CD20 positive B cells in the lymph node biopsy or other lymphoma pathology specimen.
• adequate hematologic function according to specific trial parameters.
• bidimensionally measurable disease with at least 1 lesion measuring 2.0 cm or more in a single dimension, or the patient is in the leukemic phase of the disease.
• patient has Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• patient has an estimated life expectancy of at least 3 months.
• women of childbearing potential (not surgically sterile or 2 years 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.
• men not surgically sterile or who are capable of producing offspring must practice abstinence or use a barrier method of birth control, and must agree to continue use of this method for the duration of study drug treatment and for 30 days after participation in the treatment period.

You may not qualify if:

• has received more than 3 previous standard chemotherapy regimens.
• has the blastoid subtype of mantle cell lymphoma.
• documented history of central nervous system (CNS) lymphomatous involvement.
• a history of previous high-dose chemotherapy with allogeneic stem cell transplantation (history of autologous stem cell transplantation is allowed).
• previous treatment with bendamustine.
• has an active malignancy other than MCL, or has had a malignancy other than MCL within the past 3 years, except for controlled prostate cancer without evidence of bone metastases, localized bladder cancer, cervical carcinoma in situ, breast cancer in situ, or non-melanoma skin cancer.
• has New York Heart Association (NYHA) Class III or IV heart failure, arrhythmias or unstable angina, electrocardiographic evidence of active ischemia or active conduction system abnormalities, or myocardial infarction within the last 6 months.
• has serum creatinine of more than 2.0 mg/dL or creatinine clearance of less than 30 mL/min based on the Cockcroft-Gault method or from a 24-hour urine collection.
• does not have adequate hepatic organ function as evidenced by specific trial parameters.
• has known human immunodeficiency virus (HIV) infection.
• has active hepatitis B infection. Hepatitis B surface antigen must be tested.
• a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
• has received corticosteroids within 28 days of study entry unless chronically administered (prednisone ≤20 mg/day) for indications other than lymphoma or lymphoma-related complications.
• any serious uncontrolled, medical or psychological disorder that would impair the ability of the patient to participate in or complete this study.
• any condition which places the patient at unacceptable risk or confounds the ability of the investigators to interpret study data.

Sponsors & Collaborators

• Cephalon: lead

Study Sites (13)

Teva Investigational Site 11

Fountain Valley, California, United States

Location

Teva Investigational Site 2

Los Angeles, California, United States

Location

Teva Investigational Site 35

Orlando, Florida, United States

Location

Teva Investigational Site 30

Lafayette, Indiana, United States

Location

Teva Investigational Site 20

Bethesda, Maryland, United States

Location

Teva Investigational Site 4

Hackensack, New Jersey, United States

Location

Teva Investigational Site 3

Buffalo, New York, United States

Location

Teva Investigational Site 43

Gettysburg, Pennsylvania, United States

Location

Teva Investigational Site 33

Bryan, Texas, United States

Location

Teva Investigational Site 41

Grapevine, Texas, United States

Location

Teva Investigational Site 23

Lynchburg, Virginia, United States

Location

Teva Investigational Site 6

Ottawa, Canada

Location

Teva Investigational Site 7

Toronto, Canada

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

Bendamustine Hydrochloride; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; 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; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

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 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2009
• First Posted: May 1, 2009
• Study Start: June 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: May 1, 2014
• Last Updated: November 4, 2014
• Results First Posted: October 22, 2014

Record last verified: 2014-10

Locations

US (11); CA (2)