Trial Information

Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Myelogenous Leukemia in Remission Using HLA-Matched Sibling Donors, HLA-Matched Unrelated Donors, or HLA-Mismatched Familial Donors - A Phase 2 Study

OBJECTIVES:

Primary

- Evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) or
bone marrow transplantation (BMT) from a HLA-matched sibling donor, HLA-matched
unrelated donor, or HLA-mismatched familial donor, in terms of the frequency of relapse
and duration of remission, in patients with acute myeloid leukemia (AML) who have
either achieved complete remission (CR1) after induction chemotherapy or who
experienced recurrent AML then achieved second CR (CR2) after salvage chemotherapy.

Secondary

- Determine the engraftment, donor chimerism, and secondary graft failure in these
patients.

- Assess acute and chronic graft-vs-host disease, immune recovery, and infections in
these patients.

- Determine transplantation-related mortality, leukemia-free survival, and overall
survival of these patients.

OUTLINE:

- Conditioning chemotherapy and allogeneic bone marrow or hematopoietic stem cell
transplantation (HSCT): After completion of induction chemotherapy and a resulting
complete response (CR1) or salvage chemotherapy resulting in CR2, patients receive 1 of
the following conditioning regimens and transplantations determined by age,
co-morbidity, and type of available donor:

- 15 to 55 years of age without significant co-morbidity* undergoing HLA-matched
sibling bone marrow transplantation (BMT) (BuCy conditioning): Patients receive
busulfan IV once daily on days -7 to -4 and cyclophosphamide IV over 1-2 hours
once daily on days -3 and -2. Patients then undergo an allogeneic BMT on day 0.

- Older than 55 years or younger than 55 years with co-morbidity* undergoing
HLA-matched sibling BMT; patients of any age undergoing HLA-matched unrelated
HSCT; and for patients of any age undergoing HLA-mismatched familial donor HSCT
(BuFluATG conditioning): Patients receive busulfan IV once daily on days -7 and
-6, fludarabine phosphate IV over 30 minutes once daily on days -7 to -2,
anti-thymocyte globulin IV over 4 hours once daily on days -3 to -1, and
methylprednisolone IV over 30 minutes once daily on days -4 to -1. Patients then
undergo either an allogeneic BMT on day 0 or allogeneic peripheral blood
hematopoietic stem cell infusions on days 0-1 or 0-2.

NOTE: *Significant co-morbidity is defined as residual fungal or other infections in the
lung or other viscera and residual organ toxicities occurring during induction or
consolidation chemotherapy.

- GVHD prophylaxis: Patients receive cyclosporine orally or IV over 2-4 hours twice daily
beginning on day -1 followed by a taper starting on day 30 (BuFluATG conditioning) or
day 60 (BuCy conditioning). Patients also receive methotrexate IV on days 1, 3, and 6
after the last day of donor cell infusion.

- CNS prophylaxis: Patients receive intrathecal (IT) methotrexate once before
conditioning regimen. Patients receive IT methotrexate once every 2 weeks for 3 times
after transplantation and platelet recovery. Patients also receive leucovorin calcium
orally or IV over 4 hours after IT methotrexate and then once every 6 hours for a total
of 8 doses after each dose of IT methotrexate.

After completion of study therapy, patients are followed every 3 months for 3 years and then
annually.