Reduced Intensity Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Patients With Hematologic Malignancies
- To evaluate the safety and toxicity of a reduced-intensity conditioning regimen
followed by allogeneic bone marrow or peripheral blood stem cell transplantation from
an HLA-matched unrelated donor in patients with high-risk hematologic malignancies.
- To evaluate engraftment by peripheral blood chimerism analysis.
- To determine the incidence and severity of acute and chronic graft-versus-host disease
following the transplant.
- To examine the possibility of controlling hematologic malignancies by induction of a
- To determine the disease-free survival, relapse, transplant-related mortality, and
death from all causes.
- Reduced-intensity conditioning regimen: Patients receive 1 of 2 conditioning regimens
according to diagnosis.
- Regimen 1 (acute leukemia, myelodysplastic syndromes, myeloproliferative syndrome,
or chronic myelogenous leukemia): Patients receive fludarabine phosphate IV over
30 minutes and busulfan IV over 3 hours on days -6 to -3 or orally 4 times daily
on days -7 to -3.
- Regimen 2 (lymphoproliferative malignancies): Patients receive fludarabine
phosphate IV over 30 minutes and cyclophosphamide IV over 1 hour on days -5 to -3.
Patients with CD20+ malignancies also receive rituximab IV over 4-6 hours on days
-13, -6, 1, and 8.
- Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell
transplantation on day 0.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive low-dose alemtuzumab
subcutaneously on days -11 to -9 and tacrolimus IV over 24 hours beginning on day -3
and then orally twice daily beginning on day 14 and continuing until day 60, followed
by a taper until day 180 in the absence of clinically significant GVHD. Patients also
receive methotrexate on days 1, 3, and 6.
Patients who exhibit persistent mixed chimerism or disease relapse/progression despite full
withdrawal of immunosuppression may receive up to 3 donor lymphocyte infusions.
Blood samples are taken on days 30, 60, and 100 and then every 4 weeks thereafter for
chimerism studies by PCR analysis.
After completion of study therapy, patients are followed periodically for up to 60 months.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Survival at day 100
Survival at Day 100
Scott R. Solomon, MD
Blood and Marrow Transplant Group of Georgia
United States: Food and Drug Administration
|Blood and Marrow Transplant Group of Georgia||Atlanta, Georgia 30342-1601|