Clinical trial NCT00553202
Conditions: Leukemia
Keywords: recurrent childhood acute myeloid leukemia childhood myelodysplastic syndromes
Sponsor: Children's Oncology Group
Start date: 2008-01-01; Completion date: 2020-03-31
Enrollment: 158 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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: Natural Killer (NK) cells from the donor's bone marrow may be important in fighting leukemia. Bone marrow donors can be selected based on the type of NK cells they have, specifically the killer immunoglobulin receptor (KIR) type. This study provides information on KIR type from potential donors, which can be used in selecting the bone marrow donor. This phase II trial of unrelated donor stem cell transplant in patients with high risk AML (monosomy 7, -5/5q-, high FLT3-ITD AR, or refractory or relapsed AML) in which KIR typing of the patients and potential donors will be available to the treating transplant physician at the time of donor selection.

Detailed description:
OBJECTIVES:

* 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) transplantation: 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.

Arms: arm 1: 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.

Patients undergo allogeneic hematopoietic stem cell transplantation (SCT) or allogeneic bone marrow transplantation (BMT) on day 0.

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 pharmacological study objectives
Interventions: intervention 1: anti-thymocyte globulin intervention 2: busulfan intervention 3: cyclophosphamide intervention 4: cyclosporine intervention 5: methotrexate intervention 6: methylprednisolone intervention 7: tacrolimus intervention 8: laboratory biomarker analysis intervention 9: pharmacological study intervention 10: allogeneic bone marrow transplantation intervention 11: allogeneic hematopoietic stem cell transplantation
Intervention descriptions: intervention 1: Given IV intervention 2: Given IV intervention 3: Given IV intervention 4: Given IV or orally intervention 5: Given IV intervention 6: Given IV intervention 7: Given IV intervention 8: Correlative studies intervention 9: Correlative studies intervention 10: allogeneic bone marrow transplantation intervention 11: Undergo allogeneic hematopoietic SCT

Protocol documents: