Diffuse Large B Cell Non-Hodgkin's Lymphoma in the Vulnerable/Frail Elderly. A Multicentric Randomized Phase II Trial (FRAIL-06)
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
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.
Studieöversikt
Status
Betingelser
Detaljerad beskrivning
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.
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 2
Kontakter och platser
Studieorter
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Bordeaux, Frankrike, 33076
- Institut Bergonié
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Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
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
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: 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.
|
Givet IV
Givet IV
Givet IV
Ges oralt
Ges subkutant
Ges subkutant
|
|
Experimentell: 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.
|
Givet IV
Givet IV
Givet IV
Ges oralt
Ges subkutant
Ges subkutant
Given IV
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
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Number of Participants in Complete Remission 6 Months After Randomization
Tidsram: 6 months after randomization
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Complete remission [CR] is defined according to Cheson criteria. CR requires the following:
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6 months after randomization
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Number of Participants With Severe Toxicity
Tidsram: 6 months after randomization
|
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
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Overall Survival Time
Tidsram: from randomization, up to 5 years
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OS is defined as the delay between the date of randomization and the date of death
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from randomization, up to 5 years
|
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Progression-free Survival Time
Tidsram: from randomization, up to 5 years
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Delay between the date of randomization and the date of progression or death.
Progression is defined according to the Cheson criteria.
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from randomization, up to 5 years
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Samarbetspartners och utredare
Sponsor
Samarbetspartners
Utredare
- Huvudutredare: Pierre Soubeyran, MD, PhD, Institut Bergonié
Studieavstämningsdatum
Studera stora datum
Studiestart (Faktisk)
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Immunsystemets sjukdomar
- Neoplasmer efter histologisk typ
- Neoplasmer
- Lymfoproliferativa störningar
- Lymfatiska sjukdomar
- Immunproliferativa störningar
- Lymfom
- Lymfom, B-cell
- Lymfom, icke-Hodgkin
- Läkemedels fysiologiska effekter
- Molekylära mekanismer för farmakologisk verkan
- Enzyminhibitorer
- Antiinflammatoriska medel
- Antireumatiska medel
- Antineoplastiska medel
- Immunsuppressiva medel
- Immunologiska faktorer
- Tubulin modulatorer
- Antimitotiska medel
- Mitosmodulatorer
- Glukokortikoider
- Hormoner
- Hormoner, hormonsubstitut och hormonantagonister
- Antineoplastiska medel, hormonella
- Antineoplastiska medel, Alkylering
- Alkyleringsmedel
- Myeloablativa agonister
- Antineoplastiska medel, fytogena
- Topoisomeras II-hämmare
- Topoisomerasinhibitorer
- Antineoplastiska medel, immunologiska
- Antibiotika, antineoplastiska
- Cyklofosfamid
- Rituximab
- Prednison
- Doxorubicin
- Liposomal doxorubicin
- Vincristine
Andra studie-ID-nummer
- CDR0000636032
- IB-FRAIL06 (Annan identifierare: Institut Bergonié)
- INCA-RECF0892 (Annan identifierare: Institut National du Cancer)
- IB-2008-25 (Annan identifierare: Institut Bergonié)
- EUDRACT-2008-001506-16 (Annan identifierare: EUDRACT)
Läkemedels- och apparatinformation, studiedokument
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