2-Weekly CHOP Chemotherapy With Dose-Dense Rituximab for the Treatment of Patients Aged 61 to 80 Years With Aggressive CD-20 Positive B-Cell Lymphomas: A Phase-II/Pharmacokinetic Study (CHOP-R-ESC)
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.
Interventional
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
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
No
Michael G.M. Pfreundschuh, MD
Study Chair
Universitaetsklinikum des Saarlandes
Unspecified
CDR0000454505
NCT00290667
February 2004
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