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

NCT00911183 | Completed Phase 2 Results DMC

• 4 other identifiers: IB-2008-25IB-FRAIL06INCA-RECF0892EUDRACT-2008-001506-16
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants in Complete Remission 6 Months After Randomization

  Complete remission \[CR\] is defined according to Cheson criteria. CR requires the following: 1. 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. 2. 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). 3. 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. 4. 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.

  6 months after randomization

• 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.

  6 months after randomization

Secondary Outcomes (2)

• Overall Survival Time

  from randomization, up to 5 years

• Progression-free Survival Time

  from randomization, up to 5 years

Study Arms (2)

Arm I (R-COP regimen)

EXPERIMENTAL

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.

Biological: filgrastim; Biological: pegfilgrastim; Biological: rituximab; Drug: cyclophosphamide; Drug: prednisone; Drug: vincristine sulfate

Arm II (R-COPY regimen)

EXPERIMENTAL

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.

Biological: filgrastim; Biological: pegfilgrastim; Biological: rituximab; Drug: cyclophosphamide; Drug: liposome-encapsulated doxorubicin citrate; Drug: prednisone; Drug: vincristine sulfate

Interventions

filgrastim BIOLOGICAL

Given subcutaneously

Arm I (R-COP regimen); Arm II (R-COPY regimen)

pegfilgrastim BIOLOGICAL

Given subcutaneously

Arm I (R-COP regimen); Arm II (R-COPY regimen)

rituximab BIOLOGICAL

Given IV

Arm I (R-COP regimen); Arm II (R-COPY regimen)

cyclophosphamide DRUG

Given IV

Arm I (R-COP regimen); Arm II (R-COPY regimen)

liposome-encapsulated doxorubicin citrate DRUG

Given IV

Arm II (R-COPY regimen)

prednisone DRUG

Given orally

Arm I (R-COP regimen); Arm II (R-COPY regimen)

vincristine sulfate DRUG

Given IV

Arm I (R-COP regimen); Arm II (R-COPY regimen)

Eligibility Criteria

• Age: 70 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Institut Bergonié: lead
• National Cancer Institute, France: collaborator

Study Sites (1)

Institut Bergonie

Bordeaux, 33076, France

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, Large B-Cell, Diffuse

Interventions

Filgrastim; pegfilgrastim; Rituximab; Cyclophosphamide; Prednisone; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines

Results Point of Contact

• Title: Pr Pierre Soubeyran
• Organization: Institut Bergonié

p.soubeyran@bordeaux.unicancer.fr

33(0)556333333

Study Officials

• Pierre Soubeyran, MD, PhD

  Institut Bergonié

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized non-comparative phase II trial

Study Record Dates

• First Submitted: May 29, 2009
• First Posted: June 1, 2009
• Study Start: December 2, 2008
• Primary Completion: December 31, 2012
• Study Completion: January 1, 2015
• Last Updated: August 29, 2025
• Results First Posted: June 14, 2022

Record last verified: 2022-03

Locations

FR (1)