Phase II Study of Reduced-Intensity Allogeneic Stem Cell Transplant for High-Risk Chronic Lymphocytic Leukemia (CLL)
- To determine if reduced-intensity allogeneic stem cell transplantation can improve
2-year progression-free survival (PFS) of patients with chronic lymphocytic leukemia
(CLL) or small lymphocytic lymphoma (SLL) in the early disease cohort compared to
- To determine whether 2-year PFS ≥ 50% can be achieved and 2-year PFS ≤ 30% can be
excluded in patients with CLL or SLL in the advanced disease cohort.
- To assess objective response rate.
- To assess the incidence of grade 2-4 and 3-4 acute graft-vs-host disease (GVHD).
- To assess the incidence of extensive chronic GVHD.
- To assess the incidence of treatment-related mortality at 100 days and 1 year after
- To assess overall survival.
- To assess donor chimerism for CD3+ cells at 1 and 2 years after transplantation.
- To investigate the presence of donor antigen-specific T-cell clones before and after
withdrawal of immune suppression.
- To compare the relapse profiles of patients with T-cell responses against CLL to those
whose CLL cells are not reactive.
- To prospectively examine the impact of high-risk genomic features and immune-based
single nucleotide polymorphisms on response, toxicity, and 2-year PFS.
OUTLINE: This is a multicenter study.
- Preparative regimen: Patients receive 1 of 2 preparative regimens at the discretion of
the participating institution.
- Preparative regimen 1: Patients receive rituximab IV on days -7, -1, 7, and 14 and
fludarabine phosphate IV over 30 minutes and busulfan IV over 3 hours on days -5
to -2. .
- Preparative regimen 2: Patients receive rituximab IV on days -7, -1, 7, and 14,
fludarabine phosphate IV over 30 minutes on days -5 to -2, and cyclophosphamide IV
over 1-2 hours on days -5 to -3. Patients with matched unrelated donors also
receive anti-thymocyte globulin IV over 4-6 hours on days -6 to -4.
- Graft-vs-host disease (GVHD) prophylaxis: Patients who receive preparative regimen 1
may receive either GVHD prophylaxis regimen 1 or 2; patients who receive preparative
regimen 2 may only receive GVHD prophylaxis regimen 2.
- GVHD prophylaxis regimen 1: Patients receive tacrolimus either orally or IV and
oral sirolimus beginning on day -2 and continuing until day 60, followed by a
taper until day 180. Patients also receive methotrexate IV on days 1, 3, and 6.
- GVHD prophylaxis regimen 2: Patients receive tacrolimus either orally or IV
beginning on day -2 and continuing until day 60, followed by a taper until day
180. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
- Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation
on day 0.
- Maintenance therapy: Patients receive rituximab IV at 3, 6, 9, and 12 months after
Peripheral blood and bone marrow aspirate samples may be collected periodically for
correlative laboratory studies.
After completion of study treatment, patients are followed up periodically for ≥ 5 years.
Masking: Open Label, Primary Purpose: Treatment
2-year progression-free survival
Edwin P. Alyea, MD
Dana-Farber Cancer Institute
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|
|University of Chicago Cancer Research Center||Chicago, Illinois 60637|
|CCOP - Christiana Care Health Services||Wilmington, Delaware 19899|
|CCOP - North Shore University Hospital||Manhasset, New York 11030|
|Holden Comprehensive Cancer Center at University of Iowa||Iowa City, Iowa 52242-1002|
|Cleveland Clinic Taussig Cancer Center||Cleveland, Ohio 44195|
|City of Hope Comprehensive Cancer Center||Duarte, California 91010|
|Long Island Jewish Medical Center||New Hyde Park, New York 11040|
|Florida Hospital Cancer Institute at Florida Hospital Orlando||Orlando, Florida 32803-1273|
|Wake Forest University Comprehensive Cancer Center||Winston-Salem, North Carolina 27157-1096|
|UNMC Eppley Cancer Center at the University of Nebraska Medical Center||Omaha, Nebraska 68198-7680|
|New York Weill Cornell Cancer Center at Cornell University||New York, New York 10021|
|Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis||St. Louis, Missouri 63110|
|Don Monti Comprehensive Cancer Center at North Shore University Hospital||Manhasset, New York 11030|
|Oklahoma University Cancer Institute||Oklahoma City, Oklahoma 73104|
|Cancer Institute of New Jersey at Cooper - Voorhees||Voorhees, New Jersey 08043|
|Massachusetts General Hospital||Boston, Massachusetts 02114-2617|
|H. Lee Moffitt Cancer Center and Research Institute at University of South Florida||Tampa, Florida 33612|
|Tunnell Cancer Center at Beebe Medical Center||Lewes, Delaware 19958|
|Monter Cancer Center of the North Shore-LIJ Health System||Lake Success, New York 11042|
|Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center||Columbus, Ohio 43210-1240|
|Union Hospital of Cecil County||Elkton MD, Maryland 21921|
|Dana-Farber/Brigham and Women's Cancer Center||Boston, Massachusetts 02115|