Clinical trial NCT01234467: Bendamustine + Rituximab in Older Patients With Previously Untreated Diffuse Large B-cell Lymphoma
Official title: A Phase II Trial of Bendamustine in Combination With Rituximab in Older Patients With Previously Untreated Diffuse Large B-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diffuse Large B-Cell Lymphoma
Lymphoma, Diffuse Large-Cell
Diffuse Large-Cell Lymphoma
Lymphoma
Keywords: Diffuse Large B-Cell Lymphoma
Elderly
Newly Diagnosed
Lineberger Comprehensive Cancer Center
University of North Carolina
Bendamustine
Rituximab
Rituxan
Treanda
Phase 2
Geriatric
Lymphoma
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Cephalon
First posted: 2010-11-04
Enrollment: 23
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Complete Response (CR) Rate as Defined by The International Harmonization Project for Response Criteria
timeFrame: 2 years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 2 years
measure: Partial Response Rate
timeFrame: 2 years
measure: Estimate of Progression-Free Survival
timeFrame: 2 years with the median follow-up of 29 months
measure: Overall Survival
timeFrame: 2 years with the median follow-up of 29 months
measure: Evaluate the Toxicity and Tolerability of Bendamustine in Combination With Rituximab
timeFrame: Adverse events were collected while patients were on active treatment. The median treatment time was 18 weeks.
Other outcomes:
Locations:
city: Boone
country: United States
facility: Seby B. Jones Cancer Center
state: North Carolina
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Concord
country: United States
facility: Northeast Medical Center
state: North Carolina
city: Greensboro
country: United States
facility: Moses Cone Regional Cancer Center
state: North Carolina
city: Greenville
country: United States
facility: Leo Jenkins Cancer Center, East Carolina University Medical Center
state: North Carolina
city: Raleigh
country: United States
facility: Rex Healthcare
state: North Carolina
city: Washington
country: United States
facility: Marion L. Shepard Cancer Center
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Steven Park, MD
role: PRINCIPAL_INVESTIGATOR
References: