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)
18 Years
75 Years
Both
Leukemia
Trial Information
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)
OBJECTIVES:
- 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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of B-cell chronic lymphocytic leukemia
- Co-expression of CD5/CD19 or CD5/CD20 positivity, dim sIg, and CD23 positivity
- Previously untreated advanced disease defined as presence of at least 1 of the
following:
- Total tumor mass (TTM) score greater than 9
- TTM doubling time less than 12 months
- Bone marrow failure (platelet count less than 100,000/mm^3 and/or
hemoglobin less than 10 g/dL)
PATIENT CHARACTERISTICS:
Age:
- 18 to 75
Performance status:
- WHO 0-2
Life expectancy:
- Not specified
Hematopoietic:
- See Disease Characteristics
Hepatic:
- Bilirubin less than 3 times upper limit of normal (ULN)
- Hepatitis B negative
- No active hepatitis C
Renal:
- Creatinine less than 3 times ULN OR
- Creatinine clearance greater than 0.5 times normal
Cardiovascular:
- No severe cardiovascular disease
- No arrhythmia requiring chronic treatment
- No New York Heart Association class III or IV congestive heart failure
- No symptomatic ischemic heart disease
Other:
- No uncontrolled systemic infection
- HIV negative
- No prior or concurrent uncontrolled malignancy
- No prior or concurrent central nervous system or psychiatric disorders requiring
hospitalization
- No psychological, familial, sociological, or geographical condition that would
preclude study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- No prior biologic therapy
Chemotherapy:
- No prior chemotherapy
Endocrine therapy:
- Prior steroid therapy for less than 2 weeks allowed
Radiotherapy:
- No prior radiotherapy
Surgery:
- Not specified
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Principal Investigator
Branimir Jaksic, MD, PhD
Investigator Affiliation:
University of Zagreb Medical School
Authority:
United States: Federal Government
Study ID:
CDR0000068650
NCT ID:
NCT00017108
Start Date:
March 2001
Completion Date:
Related Keywords:
- Leukemia
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- B-cell chronic lymphocytic leukemia
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
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