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

Primary Purpose

Mantle Cell Lymphoma

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Bendamustine
Rituximab
Sponsored by
Cephalon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mantle Cell Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  • patient has received other investigational agent(s) within 28 days of study entry.
  • patient has received chemotherapy within the prior 28 days.
  • patient has a known hypersensitivity to bendamustine, mannitol, or rituximab.

Sites / Locations

  • Teva Investigational Site 11
  • Teva Investigational Site 2
  • Teva Investigational Site 35
  • Teva Investigational Site 30
  • Teva Investigational Site 20
  • Teva Investigational Site 4
  • Teva Investigational Site 3
  • Teva Investigational Site 43
  • Teva Investigational Site 33
  • Teva Investigational Site 41
  • Teva Investigational Site 23
  • Teva Investigational Site 6
  • Teva Investigational Site 7

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bendamustine+Rituximab

Arm Description

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).

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Kaplan-Meier Estimate for Duration of Response
Duration of response is defined as the time between the date of the first response to date of progression or death. Response is determined on the basis of the 2007 IWG criteria. 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.
Kaplan-Meier Estimate for Progression-Free Survival
Progression-free survival is defined as the time from first exposure to study medication to disease progression or relapse, or death due to any cause. Progression is defined using the 2007 International Working Group criteria, as any new lesion or increase by at least 50% of previously involved sites from nadir.
Kaplan-Meier Estimate for Overall Survival
Overall survival is defined as the time from first exposure to study medication to death, or to last date from adverse events, concomitant medications, vital signs, lost to follow-up, or last known alive, for overall survival censoring date.
Shifts in Baseline to Post-Treatment in Positron Emission Tomography (PET)
Participants had a whole-body PET at baseline and at the end of cycle 6 or the end-of-treatment visit. Negative PET refers to PET results showing no abnormal lymph nodes; conversely, positive PET refers to PET results showing abnormal lymph nodes.
Shifts in Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status
The ECOG scale is: Grade 0: Fully active, able to carry on all pre-disease activities without restriction; Grade 1: Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; Grade 2: Ambulatory and capable of all self-care but unable to work. Up and about more than 50% of waking hours; Grade 3: Capable of only limited self-care, confined to bed or chair > 50% of waking hours; Grade 4: Completely disabled. Cannot carry on any self-care. Confined to bed or Chair. The shift table compares baseline ECOG scores to the ECOG scores as of the last treatment visit.

Full Information

First Posted
April 29, 2009
Last Updated
October 28, 2014
Sponsor
Cephalon
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1. Study Identification

Unique Protocol Identification Number
NCT00891839
Brief Title
Bendamustine Hydrochloride in Combination With Rituximab in Patients With Relapsed Refractory Mantle Cell Lymphoma
Official Title
An Open-Label Study of Bendamustine Hydrochloride in Combination With Rituximab in the Treatment of Patients With Relapsed/Refractory Mantle Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
June 2009 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cephalon

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mantle Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bendamustine+Rituximab
Arm Type
Experimental
Arm Description
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).
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
bendamustine HCl, TREANDA®, CEP-18083
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
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.
Primary Outcome Measure Information:
Title
Overall Response Rate (Complete Response + Partial Response) at the End of Cycles 3 and 6 Using the 2007 International Working Group Criteria
Description
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.
Time Frame
Month 3 (end of cycle 3), Month 6 (end of cycle 6)
Secondary Outcome Measure Information:
Title
Kaplan-Meier Estimate for Duration of Response
Description
Duration of response is defined as the time between the date of the first response to date of progression or death. Response is determined on the basis of the 2007 IWG criteria. 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.
Time Frame
Day 1 up to Month 43
Title
Kaplan-Meier Estimate for Progression-Free Survival
Description
Progression-free survival is defined as the time from first exposure to study medication to disease progression or relapse, or death due to any cause. Progression is defined using the 2007 International Working Group criteria, as any new lesion or increase by at least 50% of previously involved sites from nadir.
Time Frame
Day 1 up to Month 45
Title
Kaplan-Meier Estimate for Overall Survival
Description
Overall survival is defined as the time from first exposure to study medication to death, or to last date from adverse events, concomitant medications, vital signs, lost to follow-up, or last known alive, for overall survival censoring date.
Time Frame
Day 1 up to Month 57
Title
Shifts in Baseline to Post-Treatment in Positron Emission Tomography (PET)
Description
Participants had a whole-body PET at baseline and at the end of cycle 6 or the end-of-treatment visit. Negative PET refers to PET results showing no abnormal lymph nodes; conversely, positive PET refers to PET results showing abnormal lymph nodes.
Time Frame
Baseline (Days -30 to 0), post treatment (up to Month 9, 30 days following completion of therapy)
Title
Shifts in Baseline Eastern Cooperative Oncology Group (ECOG) Performance Status
Description
The ECOG scale is: Grade 0: Fully active, able to carry on all pre-disease activities without restriction; Grade 1: Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; Grade 2: Ambulatory and capable of all self-care but unable to work. Up and about more than 50% of waking hours; Grade 3: Capable of only limited self-care, confined to bed or chair > 50% of waking hours; Grade 4: Completely disabled. Cannot carry on any self-care. Confined to bed or Chair. The shift table compares baseline ECOG scores to the ECOG scores as of the last treatment visit.
Time Frame
Day 0 (baseline) up to Month 8

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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. patient has received other investigational agent(s) within 28 days of study entry. patient has received chemotherapy within the prior 28 days. patient has a known hypersensitivity to bendamustine, mannitol, or rituximab.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sponsor's Medical Expert
Organizational Affiliation
Cephalon
Official's Role
Study Director
Facility Information:
Facility Name
Teva Investigational Site 11
City
Fountain Valley
State/Province
California
Country
United States
Facility Name
Teva Investigational Site 2
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Teva Investigational Site 35
City
Orlando
State/Province
Florida
Country
United States
Facility Name
Teva Investigational Site 30
City
Lafayette
State/Province
Indiana
Country
United States
Facility Name
Teva Investigational Site 20
City
Bethesda
State/Province
Maryland
Country
United States
Facility Name
Teva Investigational Site 4
City
Hackensack
State/Province
New Jersey
Country
United States
Facility Name
Teva Investigational Site 3
City
Buffalo
State/Province
New York
Country
United States
Facility Name
Teva Investigational Site 43
City
Gettysburg
State/Province
Pennsylvania
Country
United States
Facility Name
Teva Investigational Site 33
City
Bryan
State/Province
Texas
Country
United States
Facility Name
Teva Investigational Site 41
City
Grapevine
State/Province
Texas
Country
United States
Facility Name
Teva Investigational Site 23
City
Lynchburg
State/Province
Virginia
Country
United States
Facility Name
Teva Investigational Site 6
City
Ottawa
Country
Canada
Facility Name
Teva Investigational Site 7
City
Toronto
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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