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

Primary Purpose

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

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bendamustine
Rituximab
Sponsored by
UNC Lineberger Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diffuse Large B-Cell Lymphoma focused on measuring Diffuse Large B-Cell Lymphoma, Elderly, Newly Diagnosed, Lineberger Comprehensive Cancer Center, University of North Carolina, Bendamustine, Rituximab, Rituxan, Treanda, Phase 2, Geriatric, Lymphoma

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Seby B. Jones Cancer Center
  • University of North Carolina at Chapel Hill
  • Northeast Medical Center
  • Moses Cone Regional Cancer Center
  • Leo Jenkins Cancer Center, East Carolina University Medical Center
  • Rex Healthcare
  • Marion L. Shepard Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bendamustine, Rituximab

Arm Description

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.

Outcomes

Primary Outcome Measures

Complete Response (CR) Rate as Defined by The International Harmonization Project for Response Criteria
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.

Secondary Outcome Measures

Overall Response Rate (ORR)
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
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
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
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
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.

Full Information

First Posted
November 2, 2010
Last Updated
April 28, 2017
Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
Cephalon
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1. Study Identification

Unique Protocol Identification Number
NCT01234467
Brief Title
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

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
March 2011 (Actual)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
Cephalon

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bendamustine, Rituximab
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
TREANDA, BENDAMUSTINE HYDROCHLORIDE, (NDA) 022249
Intervention Description
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
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan, (BLA) 103705
Intervention Description
Dosage form: Intravenous Dosage: 375 mg/m2 Frequency: Day 1 of every 3 weeks of a 21 day Cycle Duration: 3-6 Cycles
Primary Outcome Measure Information:
Title
Complete Response (CR) Rate as Defined by The International Harmonization Project for Response Criteria
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
2 years
Title
Partial Response Rate
Description
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.
Time Frame
2 years
Title
Estimate of Progression-Free Survival
Description
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.
Time Frame
2 years with the median follow-up of 29 months
Title
Overall Survival
Description
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.
Time Frame
2 years with the median follow-up of 29 months
Title
Evaluate the Toxicity and Tolerability of Bendamustine in Combination With Rituximab
Description
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.
Time Frame
Adverse events were collected while patients were on active treatment. The median treatment time was 18 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Park, MD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seby B. Jones Cancer Center
City
Boone
State/Province
North Carolina
ZIP/Postal Code
28607
Country
United States
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Northeast Medical Center
City
Concord
State/Province
North Carolina
ZIP/Postal Code
28025
Country
United States
Facility Name
Moses Cone Regional Cancer Center
City
Greensboro
State/Province
North Carolina
ZIP/Postal Code
27403
Country
United States
Facility Name
Leo Jenkins Cancer Center, East Carolina University Medical Center
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27834
Country
United States
Facility Name
Rex Healthcare
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
Marion L. Shepard Cancer Center
City
Washington
State/Province
North Carolina
ZIP/Postal Code
27889
Country
United States

12. IPD Sharing Statement

Links:
URL
http://unclineberger.org/
Description
Lineberger Comprehensive Cancer Center website

Learn more about this trial

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

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