Donor Stem Cell Transplant in Treating Young Patients With Acute Myeloid Leukemia With Monosomy 7, -5/5q-, High FLT3-ITD AR, or Refractory or Relapsed Acute Myelogenous Leukemia
RATIONALE: Giving chemotherapy before a donor stem cell transplant using stem cells that closely match the patient's stem cells, helps stop the growth of cancer cells. It also stops 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 antithymocyte globulin before transplant and cyclosporine, tacrolimus, and methotrexate before and after transplant may stop this from happening.
PURPOSE: This phase II trial is studying donor stem cell transplant to see how well it works in treating young patients with acute myeloid leukemia with monosomy 7, -5/5q-, high FLT3-ITD AR, or refractory or relapsed acute myelogenous leukemia.
Biological: anti-thymocyte globulin
Other: laboratory biomarker analysis
Other: pharmacological study
Procedure: allogeneic bone marrow transplantation
Procedure: umbilical cord blood transplantation
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Killer Immunoglobulin-like Receptor (KIR) Incompatible Unrelated Donor Hematopoietic Cell Transplantation (SCT) for AML With Monosomy 7, -5/5q-, High FLT3-ITD AR, or Refractory and Relapsed Acute Myelogenous Leukemia (AML) in Children: A Children's Oncology Group (COG) Study|
- Overall survival [ Designated as safety issue: No ]
- Disease-free survival [ Designated as safety issue: No ]
- Acute and chronic graft-versus-host disease [ Designated as safety issue: No ]
- Relapse [ Designated as safety issue: No ]
- Transplant-related mortality [ Designated as safety issue: No ]
- Time to NK cell reconstitution [ Designated as safety issue: No ]
- Time to the donor-specific NK-cell receptor expression [ Designated as safety issue: No ]
- Cumulative incidence of donor-receptor reconstitution [ Designated as safety issue: No ]
|Study Start Date:||January 2008|
|Estimated Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
- To define the relationship between the status of donor NK-cell receptor and patient outcomes after killer immunoglobulin-like receptor-incompatible unrelated donor (URD) and umbilical cord blood (UCB) hematopoietic cell transplantation (HCT) in young patients with acute myeloid leukemia with monosomy 7, -5/5q-, high FLT3 internal tandem duplication allelic ratio (High-FLT3-ITD AR), or refractory or relapsed acute myelogenous leukemia.
- To correlate the relationships between factors affecting NK receptor status and clinical events.
- To assess NK-cell development after URD and UCB HCT in patients with poor prognosis AML.
- To evaluate NK-cell reconstitution and receptor-acquisition pattern in these patients.
OUTLINE: This is a multicenter study.
Preparative regimen: Patients receive 1 of the following regimens:
- Hematopoietic stem cell transplantation (SCT): Patients receive busulfan IV 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 over 4 hours on days -3 to -1, and methylprednisolone IV on days -3 to -1.
- Umbilical cord blood (UCB) transplantantation: Conditioning regimen, infusion procedures, and post-transplant immunoprophylaxis for patients with an UCB donor are according to institutional guidelines and standards.
- Allogeneic hematopoietic stem cell transplantation (SCT) or umbilical cord blood (UCB) transplant: Patients undergo allogeneic SCT or UCB transplant on day 0.
- Graft-vs-host disease (GVHD) prophylaxis: 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 studies of natural killer cells in support of the study objectives.
After completion of study treatment, patients are followed every 6 months for 2 years and then annually for 3 years.