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

Lymphoma Clinical Trial

Official title:

A Phase II Trial of Bendamustine in Combination With Rituximab in Older Patients With Previously Untreated Diffuse Large B-cell Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01234467
• Other study ID #: LCCC 1011
• Secondary ID: 10-1405
• Status: Completed
• Phase: Phase 2
• First received: November 2, 2010
• Last updated: February 15, 2017
• Start date: November 2010
• Est. completion date: August 2016

Study information

• Verified date: February 2017
• Source: UNC Lineberger Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: August 2016
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Diffuse Large-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Diffuse Large-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin

Intervention

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

Locations

Country	Name	City	State
United States	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

Sponsors (2)

Lead Sponsor	Collaborator
UNC Lineberger Comprehensive Cancer Center	Cephalon

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete response (CR) rate as defined by The International Harmonization Project for Response Criteria		2 years
Secondary	Overall response rate (ORR, CR + PR)	The CR and ORR rates will be estimated and 95% confidence interval computed	2 years
Secondary	Estimate the disease-free survival (DFS), progression-free and overall survival	Progression-free survival will be summarized using the Kaplan-Meier method.	3 years
Secondary	Evaluate the toxicity and tolerability of bendamustine in combination with rituximab		3 years

External Links

•   Lineberger Comprehensive Cancer Center website