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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Cephalon
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01234467
First received: November 2, 2010
Last updated: December 2, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Diffuse Large B-Cell Lymphoma
Lymphoma, Diffuse Large-Cell
Diffuse Large-Cell Lymphoma
Lymphoma
Drug: Bendamustine
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of Bendamustine in Combination With Rituximab in Older Patients With Previously Untreated Diffuse Large B-cell Lymphoma

Resource links provided by NLM:


Further study details as provided by UNC Lineberger Comprehensive Cancer Center:

Primary Outcome Measures:
  • Complete response (CR) rate as defined by The International Harmonization Project for Response Criteria [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall response rate (ORR, CR + PR) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    The CR and ORR rates will be estimated and 95% confidence interval computed

  • Estimate the disease-free survival (DFS), progression-free and overall survival [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    Progression-free survival will be summarized using the Kaplan-Meier method.

  • Evaluate the toxicity and tolerability of bendamustine in combination with rituximab [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 37
Study Start Date: November 2010
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bendamustine, Rituximab Drug: 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
Other Names:
  • TREANDA
  • BENDAMUSTINE HYDROCHLORIDE
  • (NDA) 022249
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
Other Names:
  • Rituxan
  • (BLA) 103705

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.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01234467

Locations
United States, North Carolina
Seby B. Jones Cancer Center
Boone, North Carolina, United States, 28607
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
Northeast Medical Center
Concord, North Carolina, United States, 28025
Moses Cone Regional Cancer Center
Greensboro, North Carolina, United States, 27403
Leo Jenkins Cancer Center, East Carolina University Medical Center
Greenville, North Carolina, United States, 27834
Rex Healthcare
Raleigh, North Carolina, United States, 27607
Marion L. Shepard Cancer Center
Washington, North Carolina, United States, 27889
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Cephalon
Investigators
Principal Investigator: Steven Park, MD University of North Carolina, Chapel Hill
  More Information

Additional Information:
No publications provided

Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01234467     History of Changes
Other Study ID Numbers: LCCC 1011, 10-1405
Study First Received: November 2, 2010
Last Updated: December 2, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by UNC Lineberger Comprehensive Cancer Center:
Diffuse Large B-Cell Lymphoma
Elderly
Newly Diagnosed
Lineberger Comprehensive Cancer Center
University of North Carolina
Bendamustine
Rituximab
Rituxan
Treanda
Phase 2
Geriatric
Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bendamustine
Rituximab
Nitrogen Mustard Compounds
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 28, 2014