Rituximab and Combination Chemotherapy in Treating Older Patients With Previously Untreated B-Cell Lymphoma
- Conditions
- Lymphoma
- Interventions
- Biological: pegfilgrastimBiological: rituximabOther: pharmacological studyRadiation: radiation therapy
- Registration Number
- NCT00290667
- Lead Sponsor
- German High-Grade Non-Hodgkin's Lymphoma Study Group
- Brief Summary
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some find cancer cells and kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. Drugs used in chemotherapy, such as cyclophosphamide, doxorubicin, vincristine, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating older patients with previously untreated B-cell lymphoma.
- Detailed Description
OBJECTIVES:
Primary
* Determine a pharmacokinetic profile for pharmacokinetics-based or rituximab within a CHOP-14 regimen comprising cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone in elderly patients with previously untreated aggressive B-cell lymphoma.
* To determine whether increased single-doses of rituximab for males can compensate their lower serum levels.
* Evaluate the safety and toxicity profile of this regimen in male patients.
Secondary
* Determine the rate of complete responses, primary progressions under therapy, event-free survival, progression-free survival, and overall survival in patients treated with this regimen.
* Determine the rate of primary progression in patients treated with this regimen.
OUTLINE: This is a multicenter study. All patients undergo the following treatment.
* Prephase treatment: Patients receive vincristine subcutaneously on day -6 and oral prednisone on days -6 to 0.
* Immunochemotherapy and radiotherapy: Patients receive CHOP chemotherapy comprising cyclophosphamide IV over 15 minutes, doxorubicin hydrochloride IV, and vincristine IV on day 1 and oral prednisone once daily on days 1-5. Patients also receive pegfilgrastim subcutaneously on days 4, 18, 32, 46, 60, and 74. Treatment with CHOP chemotherapy repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who show no response after course 4 of CHOP chemotherapy proceed to salvage chemotherapy off study.
Patients are evaluated 2-4 weeks after completion of CHOP. Patients with initial bulky disease (i.e., diameter ≥ 7.5 cm) or extranodal involvement AND achieving complete remission (CR), unconfirmed CR (CRu), or partial remission undergo radiotherapy 5 days a week for 4 weeks. Patients who do not achieve CR or CRu 2 months after completion of radiotherapy proceed to salvage chemotherapy off study.
Patients are then stratified according to center, International Prognostic Index (1-2 vs 3-5), disease involvement (bulky vs extranodal vs bulky and/or extranodal), age (61-70 years old vs 71-80 years old), and gender. Patients are randomized to 1 of 2 treatment arms.
* Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.
* Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.
Some patients undergo blood sample collection periodically during and after treatment for pharmacokinetic studies.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then once a year therafter.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 586
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Interventional: CHOP-14 + 8 x 2-weekly rituximab rituximab Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x 2-weekly rituximab radiation therapy Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x dose-dense rituximab prednisone Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x 2-weekly rituximab pegfilgrastim Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x 2-weekly rituximab pharmacological study Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x dose-dense rituximab pegfilgrastim Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x dose-dense rituximab doxorubicin hydrochloride Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x dose-dense rituximab pharmacological study Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x dose-dense rituximab rituximab Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x 2-weekly rituximab vincristine sulfate Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x dose-dense rituximab cyclophosphamide Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x dose-dense rituximab vincristine sulfate Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x dose-dense rituximab radiation therapy Arm II (pharmacokinetic-based dose-dense rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days -1, 0, 3, 7, 14, 21, 28, and 42. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x 2-weekly rituximab doxorubicin hydrochloride Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x 2-weekly rituximab cyclophosphamide Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course. Interventional: CHOP-14 + 8 x 2-weekly rituximab prednisone Arm I (2-weekly rituximab): Patients receive rituximab IV 375 mg/m\^2 (females) and 500 mg/m\^2 (males) over 4 hours on days 0, 14, 28, 42, 56, 70, 84, and 98. Patients also receive pegfilgrastim subcutaneously on day 4 of each course.
- Primary Outcome Measures
Name Time Method Pharmacokinetics (in first 20 patients of each cohort with a distinct variation of the rituximab schedule) assessed on days -4, -1, 10, 29, 57, 99, 155, 239, 267, 295, 407, and 491 of treatment -4 to 491 days of treatment Toxicity assessed by NCI criteria, adverse events, serious adverse events, protocol adherence, and treatment-related deaths at 3 months after study completion 3 months after study completion Safety and treatment related deaths at 3 months after study completion 3 months after study completion
- Secondary Outcome Measures
Name Time Method Survival time life-long Progression rate life-long Time to treatment failure assessed at 2 years within the study and periodically thereafter at 2 years within the study and periodically thereafterlif Complete response rate assessed at 2 years within the study and periodically thereafter at 2 years within the study and periodically thereafter Progression-free survival life-long
Trial Locations
- Locations (331)
University Hospital Brno
🇨🇿Brno, Czechia
Charles University Hospital
🇨🇿Prague 5, Czechia
Hopital Debrousse
🇫🇷Lyon, France
Haematologisch Onkologische Praxis
🇩🇪Aachen, Germany
Ostalb-Klinikum Aalen
🇩🇪Aalen, Germany
Klinikum St. Marien
🇩🇪Amberg, Germany
Gemeinschaftspraxis Fuer Innere Medizin, Haematologie Und Internistische Onkologie
🇩🇪Ansbach, Germany
Specialist Practice for Oncology
🇩🇪Aschaffenburg, Germany
II. Medizinische Klinik
🇩🇪Aschaffenburg, Germany
Haematologische Praxis
🇩🇪Weiden, Germany
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