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)
- 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
- 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
PROJECTED ACCRUAL: Approximately 470 patients will be accrued for this study within 4.7
Allocation: Randomized, Primary Purpose: Treatment
Branimir Jaksic, MD, PhD
University of Zagreb Medical School
United States: Federal Government