Unrecognized Condition: Mature B or T-cell Neoplasm Clinical Trial
Official title:
Randomized Trial of Cyclosporine + CAMPATH-1H (ALEMTUZUMAB) vs. Cyclosporine + METHOTREXATE in Patients Diagnosed With Mature B-cell Neoplasms - Chronic Lymphocytic Leukemia and Low-grade Lymphomas - Receiving Allogeneic Hematopoietic Stem Cell Transplantation With Nonmyeloablative Conditioning Regimen
The primary aim of the study was to compare the efficacy of the procedure in terms of
event-free survival between patients receiving cyclosporine (CsA) plus either alemtuzumab
(CAMPATH-1H ) or methotrexate (MTX) after matched related donor allo-reduced intensity
conditioning. Secondary aims were: 1. To compare the incidence of infections and
transplant-related mortality between the two arms; 2. to compare the incidence of acute and
chronic GVHD 3. to evaluate hematologic and immunologic reconstitution and evolution of
chimerism and residual disease.
Patients were randomly assigned to received cyclosporine plus alemtuzumab or cyclosporine
plus MTX and were stratified according to diagnosis: Chronic lymphocytic leukemia or Low
grade- non-Hodgkin's lymphoma.
All patients received the same reduced-intensity conditioning (RIC) scheme based on
fludarabine 150mg/m2 (30 mg/m2/day everyday from -8 to -4) plus melphalan 140mg/m2 (70
mg/m2/day everyday from -3 to -2). Regarding the GVHD prophylaxis, patients in group 1 (n=17)
received CsA 1 mg/kg intravenously starting on day -7 and 2/mg/Kg from day -1 plus
alemtuzumab administered at a dose of 20 mg IV on -8 to -4 whereas in group 2 (n=23) pts
received CsA at same doses as group 1 plus MTX given at a dose of 15 mg/m2 intravenously on
days 1 and 10 mg/m2 on days 3, 6 and 11, followed by folinic acid rescue (15 mg in +1 and 10
mg in +3, +6 and +11 intravenously every 6 hours for 4 doses starting 24 hours after each
dose of MTX).
Acute and chronic GVHD were similarly graded by established criteria [20, 21]. In patients
receiving alemtuzumab, CsA was suspended by day +130. They also received donor lymphocyte
infusion (DLI) at a dose of 1 x 107 cluster of differentiation 3 / kg on day +180 in case of
active disease, persistence of minimal residual disease detected by flow cytometry or mixed
chimerism and no GVHD. In case mixed chimerism, donor lymphocyte infusion was performed if
patient hematopoiesis progressively increased. In patients receiving CsA + MTX, CsA was
suspended by day +180. These patients received DLI only in situations specified above.
The statistical analysis has been designed to identify a 20% difference in terms of
disease-free survival (based on the increased incidence of relapse in patients receiving
T-cell depletion).
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