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Diffuse Large B Cell Non-Hodgkin's Lymphoma in the Vulnerable/Frail Elderly. A Multicentric Randomized Phase II Trial (FRAIL-06)

Primary Purpose

Lymphoma

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
filgrastim
pegfilgrastim
rituximab
cyclophosphamide
liposome-encapsulated doxorubicin citrate
prednisone
vincristine sulfate
Sponsored by
Institut Bergonié
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma

Eligibility Criteria

70 Years - 120 Years (Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

  • Diagnosis of diffuse large B-cell non-Hodgkin lymphoma

    • Stage II, III, or IV disease (according to the WHO classification), including all morphological and clinical variants

      • No Burkitt-like lymphoma (presence of small cells in the bone marrow biopsy allowed)
    • CD20+ disease
  • Has ≥ 1 measurable target lesion ≥ 1.1 cm (according to the International Workshop Criteria)
  • Poor physiological status, as defined by ≥ 1 of the following criteria:

    • WHO performance status 3
    • Clinical evaluation and measurement of LVEF that would preclude doxorubicin administration (i.e., LVEF < 50%)
    • Creatinine clearance < 50 mL/min
    • Serum bilirubin > 30 μmol/L
    • Severe comorbidity that would preclude the use of CHOP chemotherapy
  • Ineligible for standard R-CHOP therapy
  • No cerebral or meningeal involvement

PATIENT CHARACTERISTICS:

  • WHO performance status 0-3
  • ANC > 750/mm^3
  • Platelet count > 50,000/mm^3
  • LVEF > 35%
  • Able to receive either R-COP or R-COPY therapy
  • No congestive heart failure, serious arrhythmia, or myocardial infarction within the past 6 months
  • No other malignancy within the past 5 years except for adequately treated basal cell carcinoma of the skin or curatively treated carcinoma in situ of the cervix
  • No active infection
  • No active viral hepatitis B or C by serology
  • No known HIV positivity
  • No hypersensitivity to rituximab, any of its excipients, or to murine proteins
  • No documented history of allergy to eggs or egg products
  • No psychological, familial, sociological, or geographical condition that would preclude compliance with study treatment or follow-up schedule

PRIOR CONCURRENT THERAPY:

  • No prior therapy for this cancer
  • No prior anthracycline administration with a cumulative dose > 240 mg/m² of doxorubicin hydrochloride or > 400 mg/m² of epirubicin hydrochloride
  • More than 30 days since prior participation in another clinical trial involving investigational drugs
  • No other concurrent antineoplastic agents

Sites / Locations

  • Institut Bergonie

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Arm I (R-COP regimen)

Arm II (R-COPY regimen)

Arm Description

Patients receive rituximab IV, cyclophosphamide IV, and vincristine sulfate IV on day 1. Patients also receive oral prednisone on days 1-5 and filgrastim subcutaneously (SC) on days 8-14 or pegfilgrastim SC on day 2. Treatment repeats every 21 days for at least 3 courses.

Patients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses.

Outcomes

Primary Outcome Measures

Number of Participants in Complete Remission 6 Months After Randomization
Complete remission [CR] is defined according to Cheson criteria. CR requires the following: Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities. All lymph nodes and nodal masses must have regressed to normal size. Previously involved nodes that were 1.1 to 1.5 cm in their greatest transverse diameter before treatment must have decreased to ≤1 cm in their greatest transverse diameter after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD). The spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and must not be palpable on physical examination. If the bone marrow was involved by lymphoma before treatment, the infiltrate must be cleared on repeat bone marrow aspirate and biopsy of the same site.
Number of Participants With Severe Toxicity
Severe toxicity, defined as febrile neutropenia or toxic death. Febrile neutropenia is defined in the International CTC toxicity scale as "fever of unknown origin without clinically or microbiologically documented infection: neutrophils < 1.0 x 109/l and fever ≥ 38.5° C. Toxic death is defined as any death which occur during treatment (from day 1 of the first cycle of chemotherapy up to day 30 of the last cycle) and is not related to lymphoma.

Secondary Outcome Measures

Overall Survival Time
OS is defined as the delay between the date of randomization and the date of death
Progression-free Survival Time
Delay between the date of randomization and the date of progression or death. Progression is defined according to the Cheson criteria.

Full Information

First Posted
May 29, 2009
Last Updated
March 10, 2022
Sponsor
Institut Bergonié
Collaborators
National Cancer Institute, France
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1. Study Identification

Unique Protocol Identification Number
NCT00911183
Brief Title
Diffuse Large B Cell Non-Hodgkin's Lymphoma in the Vulnerable/Frail Elderly. A Multicentric Randomized Phase II Trial
Acronym
FRAIL-06
Official Title
Diffuse Large B Cell Non-Hodgkin's Lymphoma in the Vulnerable/Frail Elderly. A Multicentric Randomized Phase II Trial With Emphasis on Geriatric Assessment and Quality of Life
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
December 2, 2008 (Actual)
Primary Completion Date
December 31, 2012 (Actual)
Study Completion Date
January 1, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Bergonié
Collaborators
National Cancer Institute, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, prednisone, and liposome-encapsulated doxorubicin citrate, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether rituximab and combination chemotherapy are more effective when given together with or without liposome-encapsulated doxorubicin citrate in treating older patients with diffuse large B-cell non-Hodgkin lymphoma. PURPOSE: This randomized phase II trial is studying the side effects of giving rituximab together with cyclophosphamide, vincristine sulfate, and prednisone with or without liposome-encapsulated doxorubicin citrate and to see how well it works in treating older patients with stage II, stage III, or stage IV diffuse large B-cell non-Hodgkin lymphoma.
Detailed Description
OBJECTIVES: Primary To assess the therapeutic efficacy of rituximab, cyclophosphamide, vincristine sulfate, and prednisone with vs without liposome-encapsulated doxorubicin citrate, in terms of complete remission rate at 6 months, in vulnerable or frail elderly patients with stage II, III, or IV diffuse large B-cell non-Hodgkin lymphoma. To assess the safety of these regimens in these patients. Secondary To evaluate the progression-free survival, event-free survival, and overall survival rates at 6 and 24 months in patients treated with these regimens. To evaluate the overall response rate at 6 and 24 months in patients treated with these regimens. To evaluate the duration of complete remission in patients treated with these regimens. To evaluate the acute side effects (according to the International CTC scale) of these regimens in these patients. To evaluate the geriatric condition and quality of life of patients treated with these regimens. OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms. Arm I (R-COP regimen): Patients receive rituximab IV, cyclophosphamide IV, and vincristine sulfate IV on day 1. Patients also receive oral prednisone on days 1-5 and filgrastim subcutaneously (SC) on days 8-14 or pegfilgrastim SC on day 2. Treatment repeats every 21 days for at least 3 courses. Arm II (R-COPY regimen): Patients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses. After 3 courses of R-COP or R-COPY, patients undergo evaluation. Patients with disease progression or a response of < 25% are removed from the study. Patients with a response of ≥ 25% receive 3 more courses of R-COP or R-COPY, followed by rituximab IV alone on day 1 of courses 7 and 8 in the absence of disease progression or unacceptable toxicity. After the completion of chemotherapy, some patients may undergo radiotherapy. Patients complete quality of life and geriatric assessment questionnaires at baseline and periodically during study treatment. After completion of study treatment, patients are followed every 3 months for 1 year, every 6 months for 2 years.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
randomized non-comparative phase II trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
67 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I (R-COP regimen)
Arm Type
Experimental
Arm Description
Patients receive rituximab IV, cyclophosphamide IV, and vincristine sulfate IV on day 1. Patients also receive oral prednisone on days 1-5 and filgrastim subcutaneously (SC) on days 8-14 or pegfilgrastim SC on day 2. Treatment repeats every 21 days for at least 3 courses.
Arm Title
Arm II (R-COPY regimen)
Arm Type
Experimental
Arm Description
Patients receive rituximab, cyclophosphamide, vincristine sulfate, prednisone, and filgrastim or pegfilgrastim as in arm I. Patients also receive liposome-encapsulated doxorubicin citrate IV on day 1. Treatment repeats every 21 days for at least 3 courses.
Intervention Type
Biological
Intervention Name(s)
filgrastim
Intervention Description
Given subcutaneously
Intervention Type
Biological
Intervention Name(s)
pegfilgrastim
Intervention Description
Given subcutaneously
Intervention Type
Biological
Intervention Name(s)
rituximab
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
liposome-encapsulated doxorubicin citrate
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
prednisone
Intervention Description
Given orally
Intervention Type
Drug
Intervention Name(s)
vincristine sulfate
Intervention Description
Given IV
Primary Outcome Measure Information:
Title
Number of Participants in Complete Remission 6 Months After Randomization
Description
Complete remission [CR] is defined according to Cheson criteria. CR requires the following: Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities. All lymph nodes and nodal masses must have regressed to normal size. Previously involved nodes that were 1.1 to 1.5 cm in their greatest transverse diameter before treatment must have decreased to ≤1 cm in their greatest transverse diameter after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD). The spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and must not be palpable on physical examination. If the bone marrow was involved by lymphoma before treatment, the infiltrate must be cleared on repeat bone marrow aspirate and biopsy of the same site.
Time Frame
6 months after randomization
Title
Number of Participants With Severe Toxicity
Description
Severe toxicity, defined as febrile neutropenia or toxic death. Febrile neutropenia is defined in the International CTC toxicity scale as "fever of unknown origin without clinically or microbiologically documented infection: neutrophils < 1.0 x 109/l and fever ≥ 38.5° C. Toxic death is defined as any death which occur during treatment (from day 1 of the first cycle of chemotherapy up to day 30 of the last cycle) and is not related to lymphoma.
Time Frame
6 months after randomization
Secondary Outcome Measure Information:
Title
Overall Survival Time
Description
OS is defined as the delay between the date of randomization and the date of death
Time Frame
from randomization, up to 5 years
Title
Progression-free Survival Time
Description
Delay between the date of randomization and the date of progression or death. Progression is defined according to the Cheson criteria.
Time Frame
from randomization, up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
70 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of diffuse large B-cell non-Hodgkin lymphoma Stage II, III, or IV disease (according to the WHO classification), including all morphological and clinical variants No Burkitt-like lymphoma (presence of small cells in the bone marrow biopsy allowed) CD20+ disease Has ≥ 1 measurable target lesion ≥ 1.1 cm (according to the International Workshop Criteria) Poor physiological status, as defined by ≥ 1 of the following criteria: WHO performance status 3 Clinical evaluation and measurement of LVEF that would preclude doxorubicin administration (i.e., LVEF < 50%) Creatinine clearance < 50 mL/min Serum bilirubin > 30 μmol/L Severe comorbidity that would preclude the use of CHOP chemotherapy Ineligible for standard R-CHOP therapy No cerebral or meningeal involvement PATIENT CHARACTERISTICS: WHO performance status 0-3 ANC > 750/mm^3 Platelet count > 50,000/mm^3 LVEF > 35% Able to receive either R-COP or R-COPY therapy No congestive heart failure, serious arrhythmia, or myocardial infarction within the past 6 months No other malignancy within the past 5 years except for adequately treated basal cell carcinoma of the skin or curatively treated carcinoma in situ of the cervix No active infection No active viral hepatitis B or C by serology No known HIV positivity No hypersensitivity to rituximab, any of its excipients, or to murine proteins No documented history of allergy to eggs or egg products No psychological, familial, sociological, or geographical condition that would preclude compliance with study treatment or follow-up schedule PRIOR CONCURRENT THERAPY: No prior therapy for this cancer No prior anthracycline administration with a cumulative dose > 240 mg/m² of doxorubicin hydrochloride or > 400 mg/m² of epirubicin hydrochloride More than 30 days since prior participation in another clinical trial involving investigational drugs No other concurrent antineoplastic agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pierre Soubeyran, MD, PhD
Organizational Affiliation
Institut Bergonié
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institut Bergonie
City
Bordeaux
ZIP/Postal Code
33076
Country
France

12. IPD Sharing Statement

Learn more about this trial

Diffuse Large B Cell Non-Hodgkin's Lymphoma in the Vulnerable/Frail Elderly. A Multicentric Randomized Phase II Trial

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