Chlorambucil in Treating Patients With Advanced Chronic Lymphocytic Leukemia
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. It is not yet known which chlorambucil regimen is more effective in treating advanced chronic lymphocytic leukemia.
PURPOSE: Randomized phase III trial to determine the effectiveness of different regimens of chlorambucil in treating patients who have advanced chronic lymphocytic leukemia.
Drug: fludarabine phosphate
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||Low Dose Chlorambucil Maintenance Vs. No Treatment Following High-Dose Chlorambucil Induction In Patients With Advanced B-Chronic Lymphocytic Leukemia. A Randomized Phase III Study Of The EORTC LG (CLL-3)|
|Study Start Date:||March 2001|
- Compare overall and disease-related survival of patients with B-cell chronic lymphocytic leukemia treated with high-dose chlorambucil induction therapy with or without low-dose chlorambucil maintenance therapy.
- Compare the time to salvage treatment in these patients treated with these regimens.
- Compare the toxic effects of these regimens in these patients.
- Compare the treatment-related mortality of these patients treated with these regimens.
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to participating center, time to complete response (before 12 weeks vs after 12 weeks vs partial response), and cytopenia at diagnosis (Binet stage A+B vs C).
All patients receive induction therapy comprising high-dose oral chlorambucil daily. Treatment continues until achievement of complete response or a maximum of 24 weeks in the absence of disease progression or unacceptable toxicity.
Patients who respond to induction therapy are randomized to 1 of 2 treatment arms for maintenance therapy.
- Arm I: Patients receive low-dose oral chlorambucil twice a week. Therapy continues for up to 5 years in the absence of disease progression or unacceptable toxicity. If disease progression occurs, then patients may proceed to salvage therapy.
- Arm II: Patients receive no maintenance therapy. If disease progresses, patients receive induction therapy again. If disease does not respond to re-induction therapy, then patients may proceed to salvage therapy.
- Salvage therapy: Patients with progressive disease during maintenance therapy receive fludarabine IV daily and cyclophosphamide IV daily on days 1-3. Treatment repeats every 4 weeks for 3-6 courses.
Patients are followed monthly for 3 months, every 2 months for 6 months, and then every 3 months thereafter.
PROJECTED ACCRUAL: Approximately 470 patients will be accrued for this study within 4.7 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00017108
|Hopital Universitaire Erasme|
|Brussels, Belgium, 1070|
|Cliniques Universitaires Saint-Luc|
|Brussels, Belgium, 1200|
|Hopital de Jolimont|
|Haine Saint Paul, Belgium, 7100|
|University Hospital - Olomouc|
|Olomouc, Czech Republic, 775 20|
|Kaposvar, Hungary, H-7400|
|Azienda Ospedaliera Papardo|
|Ospedale Sant' Eugenio|
|Rome, Italy, 00144|
|Macedonia, The Former Yugoslav Republic of|
|Clinical Center Skopje|
|Skopje, Macedonia, The Former Yugoslav Republic of, 91000|
|'s-Gravenhage, Netherlands, 2545 CH|
|Onze Lieve Vrouwe Gasthuis|
|Amsterdam, Netherlands, 1091 HA|
|Leiden University Medical Center|
|Leiden, Netherlands, 2300 CA|
|University Medical Center Nijmegen|
|Nijmegen, Netherlands, NL-6500 HB|
|Hospital Escolar San Joao|
|Porto, Portugal, 4200|
|OverallOfficial:||Branimir Jaksic, MD, PhD||University of Zagreb Medical School|