Campath 1H (Alemtuzumab) Combined With High-Dose Therapy and Autologous Stem Cell Transplantation in Chronic Lymphocytic Leukemia
18 Years
60 Years
Both
Leukemia
Trial Information
Campath 1H (Alemtuzumab) Combined With High-Dose Therapy and Autologous Stem Cell Transplantation in Chronic Lymphocytic Leukemia
OBJECTIVES:
Primary
- Determine the safety and feasibility of cytoreductive fludarabine and cyclophosphamide
followed by high-dose myeloablative therapy comprising total-body irradiation,
cyclophosphamide, and alemtuzumab in patients undergoing autologous filgrastim
(G-CSF)-mobilized peripheral blood stem cell transplantation for stage I-IV chronic
lymphocytic leukemia.
Secondary
- Determine the clinical and molecular remission rate and duration in patients treated
with this regimen.
- Determine the overall survival of patients treated with this regimen.
OUTLINE: This is a multicenter, open label, nonrandomized study. Patients are assigned to 1
of 2 cohorts according to time of enrollment.
- Cytoreductive induction therapy: All patients receive fludarabine IV and
cyclophosphamide IV on days 1-3. Treatment repeats every 28 days for 2-4 courses in the
absence of disease progression or unacceptable toxicity. Patients achieving complete
response (CR) or partial response (PR) proceed to stem cell mobilization. Patients with
stage III or IV disease at this point are removed from study.
- Stem cell mobilization: All patients receive Dexa-BEAM comprising oral dexamethasone
once daily on days 1-10; carmustine IV and melphalan IV on day 2; and cytarabine IV
twice daily and etoposide IV once daily on days 4-7. Patients also receive filgrastim
(G-CSF) subcutaneously beginning on day 8 and continuing until leukapheresis is
completed. Patients undergo peripheral blood stem cell (PBSC) harvest between days 20
and 28. Patients without an adequate number of collected PBSCs may receive a second
course of Dexa-BEAM. Patients achieving CR or very good PR proceed to high-dose
myeloablative therapy and PBSC transplantation (PBSCT) with or without consolidation
therapy.
- Consolidation therapy: Beginning between 1-2 months after completion of Dexa-BEAM,
patients in cohort 2 receive alemtuzumab IV over 2 hours on days 1, 3, 5, 8, 10, 12,
15, 17, 19, 22, 24, and 26 and then proceed to high-dose myeloablative therapy and
PBSCT within 1 month after completion of consolidation therapy. Patients in cohort 1 do
not receive consolidation therapy and proceed directly to high-dose therapy within 3
months after completion of stem cell mobilization.
- High-dose myeloablative therapy and PBSCT: Patients undergo total-body irradiation on
days -7 to -5. Patients then receive cyclophosphamide IV on days -4 and -3 and
alemtuzumab IV over 2 hours on days -10, -9, -8, -6, and -4. Patients undergo PBSCT on
day 0.
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Chronic lymphocytic leukemia (CLL), meeting 1 of the following stage criteria:
- Stage I-IV disease
- Binet stage B or C disease
- Binet stage A disease at high risk for rapid disease progression, as defined by
both of the following criteria:
- Nonnodular marrow infiltration and/or lymphocyte doubling time < 12 months
- Thymidine kinase > 7.0 U/L and/or ß-2-microglobulin > 3.5 mg/L
- Polymerase chain reaction-amplifiable clonal CDR III rearrangement of the
immunoglobulin variable heavy chain gene
- No Richter's syndrome or B-prolymphocytic leukemia
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- No concurrent disease resulting in major organ dysfunction
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No other concurrent malignancy
- No New York Heart Association class III or IV cardiac failure
- No cardiomyopathy
- No history of myocardial infarction
- No symptomatic coronary heart disease
- No severe cardiac arrhythmia
- No severe or uncontrolled hypertension
- No chronic pulmonary disease
- No pulmonary function test impairment
- No severe or uncontrolled diabetes mellitus
- Bilirubin or transaminases ≤ 1.5 times upper limit of normal
- Creatinine ≤ 1.4 mg/dL
- No cerebral dysfunction
- No severe psychiatric impairment
- No drug addiction or alcoholism
- Negative HIV
- Negative Hepatitis B or C
- No allergy to any of the protocol drugs
- No history of anaphylactic reaction to monoclonal antibodies
- No active infection
PRIOR CONCURRENT THERAPY:
- No more than 1 prior chemotherapy regimen OR chemotherapy that lasted > 6 months
- No prior radiotherapy
- No prior treatment with alemtuzumab
- No prior long-term (> 1 month) systemic corticosteroids
- No prior therapy with dexamethasone, carmustine, etoposide, cytarabine, and melphalan
(Dexa-BEAM)
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety and feasibility of CAMPATH-1H included into the myeloablative regimen (cyclophosphamide and TBI) of the CLL3 protocol monitoring of treatment related mortality and morbidity (CTC scale) continuous
Safety Issue:
Yes
Principal Investigator
Stephan Stilgenbauer, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Comprehensive Cancer Center Ulm at Universitaetsklinikum Ulm
Authority:
United States: Federal Government
Study ID:
CDR0000455093
NCT ID:
NCT00276809
Start Date:
June 2001
Completion Date:
Related Keywords:
- Leukemia
- stage 0 chronic lymphocytic leukemia
- stage I chronic lymphocytic leukemia
- stage II chronic lymphocytic leukemia
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
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