Bendamustine + Rituximab in Older Patients With Previously Untreated Diffuse Large B-cell Lymphoma
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.
|Diffuse Large B-Cell Lymphoma Lymphoma, Diffuse Large-Cell Diffuse Large-Cell Lymphoma Lymphoma||Drug: Bendamustine Drug: Rituximab||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (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|
- Complete Response (CR) Rate as Defined by The International Harmonization Project for Response Criteria [ Time Frame: 2 years ]Complete response (CR) is defined as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. The complete response rate is the percentage of participants achieving a CR.
- Overall Response Rate (ORR) [ Time Frame: 2 years ]The ORR consists of the complete response rate + the partial response rate (percentage of participants achieving a complete or partial response). Complete response is defined by The International Harmonization Project for Response Criteria as the complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. Partial response is defined as regression of measurable disease and no new sites.
- Partial Response Rate [ Time Frame: 2 years ]The percentage of participants achieving a partial response (PR). PR is defined by The International Harmonization Project for Response Criteria as regression of measurable disease and no new sites.
- Estimate of Progression-Free Survival [ Time Frame: 2 years with the median follow-up of 29 months ]Progression-free survival (PFS) will be summarized using the Kaplan-Meier method. PFS was defined as the time from the start of treatment until lymphoma progression or death as a result of any cause. Progression was defined by The International Harmonization Project for Response Criteria as any new lesion or increase by ≥50% of previously involved sites from nadir.
- Overall Survival [ Time Frame: 2 years with the median follow-up of 29 months ]This represents the Kaplan-Meier estimates of median overall survival defined as the time from start of treatment until death as a result of any cause.
- Evaluate the Toxicity and Tolerability of Bendamustine in Combination With Rituximab [ Time Frame: Adverse events were collected while patients were on active treatment. The median treatment time was 18 weeks. ]The major grade 3 or higher adverse events were haematological toxicities. The results below include common haematological and non-haematological toxicities of grade 3 or higher. A complete record of all adverse events are reported in the adverse events section. National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0 were used to assess toxicity.
|Actual Study Start Date:||March 2011|
|Study Completion Date:||August 2016|
|Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: 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.
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: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
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01234467
|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|
|Raleigh, North Carolina, United States, 27607|
|Marion L. Shepard Cancer Center|
|Washington, North Carolina, United States, 27889|
|Principal Investigator:||Steven Park, MD||University of North Carolina, Chapel Hill|