AAML05P1: Phase II Pilot Study of Killer Immunoglobulin-Like Receptor-Incompatible Unrelated Donor Hematopoietic Cell Transplantation in Young Patients With Relapsed, Refractory, or Newly Diagnosed Acute Myeloid Leukemia/ Therapy for New Diagnosis High Risk Disease
What is the purpose of this study?
1. To define the relationship between the status of donor NK-cell receptor and patient outcomes after killer immunoglobulin-like receptor-incompatible unrelated donor (URD) hematopoietic cell transplantation (HCT) in young patients with poor prognosis relapsed or refractory acute myeloid leukemia (AML) or newly diagnosed AML.
2. To assess NK-cell development after URD HCT in these patients.
Who can participate?
Diagnosis of one of the following:
- Primary refractory acute myeloid leukemia (AML) (> 5% bone marrow blasts after two cycles of induction chemotherapy)
- Newly diagnosed AML with -5/5q- or monosomy 7 in patients who have completed two cycles of induction chemotherapy
- Relapsed AML meeting the customary WHO criteria for AML
- These patients must have undergone re-induction chemotherapy
- No Fanconi anemia
- No CNS disease
- HLA-matched donor available
- Matched at HLA-A, -B, -C, and -DRB1
- Donor with the highest number of KIR-KIR ligand mismatches will be selected
- Adult Studies
- Cancer - Leukemia and Lymphoma
What is involved?
This is a multicenter study.
- Preparative regimen: Patients receive busulfan IV over 2 hours every 6 hours on days -9 to -6, high-dose cyclophosphamide IV over 1 hour on days -5 to -2, anti-thymocyte globulin IV once or twice daily on days -3 to -1, and methylprednisolone IV on days -3 to -1.
- Allogeneic hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT on day 0.
- Graft-versus-host disease (GVHD) prophylaxis (for patients undergoing bone marrow transplantation): Patients receive cyclosporine or tacrolimus IV or orally beginning on day -2 and continuing until day 50, followed by a taper until week 24. Patients also receive methotrexate IV on days 1, 3, 6, and 11.
Blood samples will be collected periodically from both patients and donors for pharmacokinetics studies and studies of natural killer cells.
After completion of study treatment, patients are followed every 6 months for 2 years and then annually for 3 years.