Bendamustine + Rituximab in Older Patients With Previously Untreated Diffuse Large B-cell Lymphoma

NCT ID: NCT01234467

Last Updated: 2017-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-03-31
• Study Completion Date: 2016-08-31

Brief Summary

The purpose of this research study is to learn about the safety of the treatment with a combination of bendamustine and rituximab and to find out what effects, both good and bad this treatment has on DLBCL. In addition to learning about the combination of bendamustine and rituximab, the researchers are interested in learning about how this cancer treatment affects daily activities. Subjects will be asked to complete a Geriatric Assessment (GA). GAs are designed to gather information on memory, nutritional status, mental health, and level of social support. GAs are also designed to help the health care team understand how well subjects can carry out their day to day activities and to briefly describe what other medical conditions subjects may have. This assessment will help the health care team understand a subject's "functional age" (the age a subject functions at) as compared to a subject's actual age.

The researchers also want to learn how chemotherapy affects the aging process in our bodies. This is done by measuring the amount of p16 in blood. Researchers want to understand if chemotherapy changes the levels of p16 in blood.

Detailed Description

This multicenter Phase II clinical study will investigate the complete response (CR) rate after therapy with bendamustine combined with rituximab in older (≥65 years old) patients with previously untreated stage II-IV DLBCL deemed poor candidates for cyclophosphamide, doxorubicin hydrochloride, vincristine (Oncovin®), prednisone, rituximab (CHOP-R); n=37. The hypothesis being tested is that this regimen will be safe and effective as frontline therapy in older DLBCL patients deemed poor candidates for CHOP-R. After 3 cycles of therapy, patients with less than a partial response (PR) will come off study, and be managed at the discretion of their treating physician. Patients who achieve a PR after 3 cycles will continue for a total of 8 cycles of therapy, while patients who achieve a CR will continue for a total of 6 cycles of therapy. Secondary objectives include overall response rates (ORR), disease-free, progression-free and overall survival, and an evaluation of the toxicity and tolerability of the regimen.

This trial also includes an exploratory analysis designed to evaluate a potential correlation between expression of the senescence marker p16INK4a and the toxicity associated with this regimen.

In addition, patients will be asked to participate in a Geriatric Assessment (GA) tool during the trial.

Conditions

Diffuse Large B-Cell Lymphoma; Lymphoma, Diffuse Large-Cell; Diffuse Large-Cell Lymphoma; Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bendamustine, Rituximab

This is a single arm intervention where patients will receive bendamustine at a dose of 120 mg/m\^2 infused over 60 minutes in days 1 and 2 of each 21 day cycle along with rituximab 375 mg/m\^2 after bendamustine on day 1 of each cycle. Patients with Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 3 at baseline were allowed to receive bendamustine at a dose of 90 mg/m\^2 daily with a dose increase to 120 mg/m\^2 daily if their ECOG improved.

Group Type: EXPERIMENTAL

Bendamustine

Intervention Type: DRUG

Dosage Form: Intravenous (60 minute infusion) Dosage: 120mg/m2 (ECOG = 0-2) or 90mg/m2 (ECOG = 3) Frequency: Day 1 and Day 2; Every 3 weeks of a 21 day cycle. Duration: 3-6 Cycles

Rituximab

Intervention Type: DRUG

Dosage form: Intravenous Dosage: 375 mg/m2 Frequency: Day 1 of every 3 weeks of a 21 day Cycle Duration: 3-6 Cycles

Interventions

Bendamustine

Dosage Form: Intravenous (60 minute infusion) Dosage: 120mg/m2 (ECOG = 0-2) or 90mg/m2 (ECOG = 3) Frequency: Day 1 and Day 2; Every 3 weeks of a 21 day cycle. Duration: 3-6 Cycles

Intervention Type: DRUG

Rituximab

Dosage form: Intravenous Dosage: 375 mg/m2 Frequency: Day 1 of every 3 weeks of a 21 day Cycle Duration: 3-6 Cycles

Intervention Type: DRUG

Other Intervention Names

TREANDA; BENDAMUSTINE HYDROCHLORIDE; (NDA) 022249; Rituxan; (BLA) 103705

Eligibility Criteria

Inclusion Criteria

• Patients with previously untreated , histologically confirmed, diffuse large B-cell lymphoma (DLBCL), immunophenotyped for CD20
• Age greater than or equal to 65 years
• Stage II-IV
• Measurable disease including lesions that can be accurately measured in 2 dimensions by CT and have a greatest transverse diameter of 1cm or greater, and/or by bone marrow histopathology.
• ECOG performance status of 0-3
• Deemed poor candidate for CHOP-R due to ejection fraction less than or equal to 45%, ECOG performance status of 2, or in the opinion of the treating physician, patient would not tolerate administration of CHOP-R chemotherapy for other reasons,
• Life expectancy of at least 3 months;
• Documented negative serologic testing for HIV, Hepatitis B (unless positive due to prior vaccination), and hepatitis C within the year prior to enrollment
• Adequate bone marrow function (without transfusion support within one week of screening) function:
• Hemoglobin > 8 g/dL
• Absolute neutrophil count (ANC) >1000 cells/mm3
• Platelet count > 75,000/mm3
• Adequate hepatic and renal function as demonstrated by:
• Aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN)
• Total serum bilirubin < 2.5 x ULN
• Serum creatinine < 1.5 x ULN
• If sexually active male of reproductive capability, has agreed to use a medically accepted form of contraception from time of enrollment to completion of all follow-up study visits
• Signed an institutional review board (IRB) approved informed consent document

Exclusion Criteria

• Central nervous system involvement by lymphoma
• History of previous allergic reactions to compounds of similar biological or chemical composition as rituximab or bendamustine
• Medical or other condition that would represent an inappropriate risk to the patient or would likely compromise achievement of the primary study objective.
• Other active malignancies (except: non-melanoma skin cancer, cervical carcinoma in situ without evidence of disease, prostatic intraepithelial neoplasia without evidence of prostate cancer)
• Patients on strong inhibitors of CYP1A2.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cephalon

INDUSTRY

Sponsor Role: collaborator

UNC Lineberger Comprehensive Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Steven Park, MD

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

Seby B. Jones Cancer Center

Boone, North Carolina, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Northeast Medical Center

Concord, North Carolina, United States

Moses Cone Regional Cancer Center

Greensboro, North Carolina, United States

Leo Jenkins Cancer Center, East Carolina University Medical Center

Greenville, North Carolina, United States

Rex Healthcare

Raleigh, North Carolina, United States

Marion L. Shepard Cancer Center

Washington, North Carolina, United States

Countries

United States

Related Links

http://unclineberger.org/

Lineberger Comprehensive Cancer Center website

Other Identifiers

10-1405

Identifier Type: OTHER

Identifier Source: secondary_id

LCCC 1011

Identifier Type: -

Identifier Source: org_study_id