A Phase II Trial of T-Cell Depleted Marrow Grafts Combined With Infusions of G-CSF Stimulated, CD34 Ceprate Stem Cell Column Selected, E-Rosette Depleted Peripheral Blood Progenitor Cells Derived From HLA Haplotype Matched Related Donors for Patients With Leukemia Lacking an HLA-Matched Related or Unrelated Donor
- Determine the potential of T-cell-depleted bone marrow and peripheral blood stem cells
(PBSC) from HLA-haplotype, partially matched related donors to induce extended
disease-free survival in patients with leukemia, lymphoblastic lymphoma,
myelodysplastic syndrome, or severe aplastic anemia who would otherwise be ineligible
for transplantation because of the lack of an HLA-identical related or unrelated donor.
- Determine the impact of filgrastim (G-CSF)-stimulated, CD34+, E-rosette and
T-cell-depleted PBSC derived from an HLA-haplotype, partially matched donor on the
incidence and quality of engraftment, kinetics, and quality of hematopoietic and
immunologic reconstitution, and incidence and severity of graft-versus-host disease
(GVHD) in these patients.
- Correlate the doses of PBSC and clonable T-cells with the incidence of engraftment,
extent of chimerism, incidence and severity of acute and chronic GVHD, characteristics
of hematopoietic and immunologic reconstitution, and overall and disease-free survival
rates at 2-4 years after transplantation in these patients.
OUTLINE: Patients are stratified by number of HLA-incompatible alleles (1 vs 2 or 3).
- Harvest: Beginning 6-10 days before transplantation, allogeneic bone marrow is
harvested and treated in vitro. Beginning 5-6 days before transplantation, filgrastim
(G-CSF)-stimulated, allogeneic peripheral blood stem cells (PBSC) are harvested,
selected for CD34+ cells, and treated in vitro. If feasible, autologous bone marrow is
harvested in the event of allogeneic graft failure.
- Myeloablation: Patients undergo total body irradiation 3 times a day on days -9 to -6,
thiotepa IV over 4 hours on days -5 and -4, and cyclophosphamide IV on days -3 and -2.
- Transplantation: CD34+, E-rosette and T-cell-depleted PBSC are infused over 15 minutes
and then T-cell-depleted bone marrow is infused over 1-5 minutes on day 0. Patients
receive G-CSF IV over 30 minutes beginning on day 1 and continuing until blood counts
recover and then tapering. Patients receive anti-thymocyte globulin IV over 4-6 hours
on days 8, 10, 12, and 14 and oral methylprednisolone on days 8-14 followed by tapered
doses on days 15-17.
- CNS prophylaxis: Beginning at least 2 months after transplantation, patients with acute
lymphocytic leukemia (ALL) and no history of CNS leukemia receive cytarabine
intrathecally (IT) monthly for 6 months and patients with ALL and a history of CNS
leukemia receive cytarabine IT monthly for 12 months.
Patients with graft failure are offered autologous bone marrow transplantation (BMT) or
second allogeneic BMT.
Patients are followed at 1, 3, 6, and 12 months and then annually for 3 years.
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
overall disease survival
2 to 4 years post transplant
Richard J. O'Reilly, MD
Memorial Sloan-Kettering Cancer Center
United States: Institutional Review Board
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|