The Unrelated Donor Marrow Transplantation Trial

Trial Information

The Unrelated Donor Marrow Transplantation Trial

OBJECTIVES: I. Compare the disease free survival of patients with leukemia, myelodysplasia,
or lymphoblastic lymphoma after treatment with conventional (non-T cell depleted) or T cell
depleted unrelated donor bone marrow transplantation. II. Compare the incidence of primary
and secondary graft failure, acute and chronic graft-vs-host disease, complications
(infection, veno-occlusive disease, interstitial pneumonitis), and relapse in these patients
after these treatments. III. Compare the incidence of other malignancies,
lymphoproliferative disorders, and post-transplant myelodysplasia in these patients after
these treatments.

OUTLINE: This is a randomized, multicenter study. Patients will be stratified according to
institution. Patients are assigned to one of two treatment arms, one with conventional bone
marrow transplantation (arm I) and one with T cell depletion of the bone marrow (arm II).
Arm I: Patients receive cyclophosphamide on days -6 and -5. Total body irradiation (TBI) is
administered on days -4 to 0, although this order may be reversed. Males with ALL receive a
testicular boost of radiation therapy. Bone marrow is infused on day 0. Patients receive
cyclosporine beginning on day -1 and methotrexate IV on days 1, 3, 6, and 11. Arm II: T cell
depletion is conducted by 2 different methods, according to the institution, and treatment
varies depending on the method used. Method I is by T10B9 depletion and Method II is by
counterflow elutriation depletion. Method I: Depending on the institution, some patients
receive TBI on days -9 to -7 (before chemotherapy) (Course I) and some receive TBI on days
-3 to -1 (after chemotherapy) (Course II). Course I also includes cytarabine IV on days -5
to -3, cyclophosphamide IV on days -2 and -1, and methylprednisolone IV on days -2 to 0 and
5-18. Bone marrow infusion is administered on day 0. Cyclosporine begins on day -1. Course
II includes cytarabine IV on days -7 to -4 and cyclophosphamide on days -6 to -5.
Methylprednisolone IV is administered on days -2 to 0 and 5-18. Bone marrow infusion is
administered on day 0. Cyclosporine begins on day 0. Method II: Preparative therapy varies
according to the disease category. Acute lymphoblastic leukemia: Patients undergo TBI on
days -7 to -4. Males receive testicular boost on day -7, and all receive electron boost to
anterior and posterior chest wall on days -5 and -4. Cyclophosphamide IV is administered on
days -3 and -2. Bone marrow infusion is administered on day 0. Acute nonlymphocytic
leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome: Patients receive
cyclophosphamide IV on days -7 and -6, followed by TBI on days -4 to -1. Bone marrow
infusion is administered on day 0. Patients receive methylprednisolone IV every 12 hr on
days -2,-1, and 5-19. Cyclosporine is administered from day -3 to day 180. All patients on
both arms receive filgrastim (granulocyte colony-stimulating factor; G-CSF) beginning on day
7 post-transplant. Patients are followed weekly for the first 14 weeks, at day 100, every 6
months for 2 years, then annually thereafter.

PROJECTED ACCRUAL: A total of 560 patients will be accrued for this study within 4 years.