Trial Information

Pilot Study on Allogeneic Stem Cell Transplantation Following Conditioning With Fludarabine and an Alkylating Agent in Patients With High-Risk Chronic Lymphocytic Leukemia

OBJECTIVES:

Primary

- Determine the feasibility and safety of induction therapy comprising fludarabine and
cyclophosphamide followed by allogeneic stem cell transplantation in patients with
high-risk B-cell chronic lymphocytic leukemia or lymphoplasmocytic lymphoma
(Waldenstrom's macroglobulinemia).

Secondary

- Determine the incidence and kinetics of clinical and molecular remissions in patients
treated with this regimen.

- Determine event-free and overall survival of patients treated with this regimen.

- Determine the duration of clinical and molecular remission in relation to the
underlying cytogenetic deviation in patients treated with this regimen.

- Determine the kinetics and extent of lympho-hematopoietic donor chimerism in patients
treated with this regimen.

OUTLINE: This is a multicenter, open-label, nonrandomized, pilot study.

- Cytoreductive therapy: Patients receive up to 3 courses of cytoreductive therapy
comprising fludarabine IV and cyclophosphamide IV on days 1-3 (with or without
rituximab IV on day 1). Patients refractory to fludarabine-containing therapy may
receive alemtuzumab IV for 12 weeks OR any other cytotoxic salvage regimen for
cytoreduction.

- Conditioning regimen: Patients receive 1 of the following conditioning regimens*:

NOTE: *Patients who did not achieve partial response after cytoreductive therapy receive
regimen 3.

- Regimen 1: Patients receive fludarabine IV and cyclophosphamide IV on days -7 to -3. If
stem cells are collected from an unrelated donor, patients also receive anti-thymocyte
globulin (ATG) IV on days -4 to -1.

- Regimen 2: Patients undergo total-body irradiation on day -9. Patients then receive
alemtuzumab IV on days -8 to -4 and fludarabine IV and cyclophosphamide IV on days -6
to -2.

- Regimen 3: Patients receive fludarabine IV on days -7 to -3, busulfan IV or orally on
days -7 to -5, and cyclophosphamide IV on days -3 to -2. If stem cells are collected
from an unrelated donor, patients also receive ATG on days -3 to -1.

- Allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo
allogeneic PBSCT on day 0. Patients receive filgrastim (G-CSF) subcutaneously
daily starting on day 5 and continuing until blood count recover.

- Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine IV
beginning on day -1 and continuing until approximately day 100. Patients treated
with conditioning regimen 1 or 3 also receive methotrexate IV on days 1, 3, and 6
OR oral mycophenolate mofetil twice daily on days 0-50. Patients with evidence of
residual disease at least 4 weeks after completion of cyclosporine undergo donor
lymphocyte infusion (DLI).

- DLI: The donor T-lymphocytes are collected from the PBSCT donor without prior
G-CSF mobilization. Patients receive DLI every 8 weeks in the presence of residual
disease and the absence of GVHD.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.