Clinical trial NCT00453388
Conditions: Acute Myeloid Leukemia in Remission de Novo Myelodysplastic Syndrome Fanconi Anemia Previously Treated Myelodysplastic Syndrome
Sponsor: Fred Hutchinson Cancer Center
Start date: 2007-02-01; Completion date: 2013-06-01
Enrollment: 6 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This phase II trial studies how well total-body irradiation (TBI) works when given together with fludarabine phosphate and cyclophosphamide followed by donor bone marrow transplant, mycophenolate mofetil, and cyclosporine in treating patients with Fanconi anemia (FA). Giving low doses of chemotherapy, such as fludarabine phosphate and cyclophosphamide, and TBI before or after a donor bone marrow transplant helps stop the growth of abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving mycophenolate mofetil and cyclosporine after the transplant may stop this from happening.

Detailed description:
PRIMARY OBJECTIVES:

I. Identify doses of total-body irradiation (TBI) that lead to sufficient probability of donor engraftment (\> 5% donor cluster of differentiation \[CD\]3 chimerism) by day +200.

II. Evaluate the probability of severe acute graft-versus-host disease.

SECONDARY OBJECTIVES:

I. Evaluate the probabilities of overall survival, regimen-related toxicity (RRT), and recurrent hematopoietic malignancy in those patients with a prior underlying history of such.

II. Examine the degree to which mixed chimerism provides for amelioration of symptoms (i.e., infections due to neutropenia, hemorrhage due to thrombocytopenia) associated with bone marrow failure.

III. Determine if the FA complementation group and % initial mosaicism predict engraftment and RRT outcomes.

OUTLINE: Patients are assigned to 1 of 4 treatment arms.

NOTE: Patients no longer receive pre-transplant cyclophosphamide as of February 2009.

After completion of study treatment, patients are followed up at 6 months and then annually thereafter.

Arms: arm 1: Patients with a history of hematologic malignancy and HLA-haploidentical donor receive fludarabine phosphate (FLU) intravenously (IV) over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF orally (PO) thrice daily (TID) on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. arm 2: Patients with no history of hematological malignancy and HLA-haploidentical donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. arm 3: Patients with history of hematologic malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD. arm 4: Patients with no history of hematological malignancy and HLA-matched unrelated donors receive FLU IV over 1 hour on days -6 to -2, and undergo TBI on day -1 and allogeneic bone marrow transplant on day 0. Patients then receive CY IV over 1 hour on days 3 and 4, MMF PO TID on days 5-35, and CSP IV or PO on days 5-84, with taper until day 180, in the absence of GVHD.
Interventions: intervention 1: Allogeneic Bone Marrow Transplantation intervention 2: Cyclophosphamide intervention 3: Cyclosporine intervention 4: Fludarabine Phosphate intervention 5: Laboratory Biomarker Analysis intervention 6: Mycophenolate Mofetil intervention 7: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation intervention 8: Total-Body Irradiation
Intervention descriptions: intervention 1: Undergo allogeneic bone marrow transplant intervention 2: Given IV intervention 3: Given IV or PO intervention 4: Given IV intervention 5: Correlative studies intervention 6: Given PO intervention 7: Undergo allogeneic stem cell transplant intervention 8: Undergo TBI

Protocol documents: