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Donor Stem Cell Transplant or Bone Marrow Transplant in Treating Patients With Acute Myeloid Leukemia in Remission

Phase 2
Completed
Conditions
Leukemia
Interventions
Biological: anti-thymocyte globulin
Procedure: allogeneic hematopoietic stem cell transplantation
Registration Number
NCT01020734
Lead Sponsor
Asan Medical Center
Brief Summary

RATIONALE: Giving chemotherapy before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and methotrexate before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well donor stem cell transplant or bone marrow transplant works in treating patients with acute myeloid leukemia in remission.

Detailed Description

OBJECTIVES:

Primary

* Evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (HSCT) or bone marrow transplantation (BMT) from a HLA-matched sibling donor, HLA-matched unrelated donor, or HLA-mismatched familial donor, in terms of the frequency of relapse and duration of remission, in patients with acute myeloid leukemia (AML) who have either achieved complete remission (CR1) after induction chemotherapy or who experienced recurrent AML then achieved second CR (CR2) after salvage chemotherapy.

Secondary

* Determine the engraftment, donor chimerism, and secondary graft failure in these patients.

* Assess acute and chronic graft-vs-host disease, immune recovery, and infections in these patients.

* Determine transplantation-related mortality, leukemia-free survival, and overall survival of these patients.

OUTLINE:

* Conditioning chemotherapy and allogeneic bone marrow or hematopoietic stem cell transplantation (HSCT): After completion of induction chemotherapy and a resulting complete response (CR1) or salvage chemotherapy resulting in CR2, patients receive 1 of the following conditioning regimens and transplantations determined by age, co-morbidity, and type of available donor:

* 15 to 55 years of age without significant co-morbidity\* undergoing HLA-matched sibling bone marrow transplantation (BMT) (BuCy conditioning): Patients receive busulfan IV once daily on days -7 to -4 and cyclophosphamide IV over 1-2 hours once daily on days -3 and -2. Patients then undergo an allogeneic BMT on day 0.

* Older than 55 years or younger than 55 years with co-morbidity\* undergoing HLA-matched sibling BMT; patients of any age undergoing HLA-matched unrelated HSCT; and for patients of any age undergoing HLA-mismatched familial donor HSCT (BuFluATG conditioning): Patients receive busulfan IV once daily on days -7 and -6, fludarabine phosphate IV over 30 minutes once daily on days -7 to -2, anti-thymocyte globulin IV over 4 hours once daily on days -3 to -1, and methylprednisolone IV over 30 minutes once daily on days -4 to -1. Patients then undergo either an allogeneic BMT on day 0 or allogeneic peripheral blood hematopoietic stem cell infusions on days 0-1 or 0-2.

NOTE: \*Significant co-morbidity is defined as residual fungal or other infections in the lung or other viscera and residual organ toxicities occurring during induction or consolidation chemotherapy.

* GVHD prophylaxis: Patients receive cyclosporine orally or IV over 2-4 hours twice daily beginning on day -1 followed by a taper starting on day 30 (BuFluATG conditioning) or day 60 (BuCy conditioning). Patients also receive methotrexate IV on days 1, 3, and 6 after the last day of donor cell infusion.

* CNS prophylaxis: Patients receive intrathecal (IT) methotrexate once before conditioning regimen. Patients receive IT methotrexate once every 2 weeks for 3 times after transplantation and platelet recovery. Patients also receive leucovorin calcium orally or IV over 4 hours after IT methotrexate and then once every 6 hours for a total of 8 doses after each dose of IT methotrexate.

After completion of study therapy, patients are followed every 3 months for 3 years and then annually.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
263
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
transplantationanti-thymocyte globulinperform allogeneic HCT for patients with AML in CR1; then analyze various pre-transplantation variable, including donor type, for correlation to outcomes
transplantationallogeneic hematopoietic stem cell transplantationperform allogeneic HCT for patients with AML in CR1; then analyze various pre-transplantation variable, including donor type, for correlation to outcomes
transplantationfludarabine phosphateperform allogeneic HCT for patients with AML in CR1; then analyze various pre-transplantation variable, including donor type, for correlation to outcomes
transplantationcyclosporineperform allogeneic HCT for patients with AML in CR1; then analyze various pre-transplantation variable, including donor type, for correlation to outcomes
transplantationbusulfanperform allogeneic HCT for patients with AML in CR1; then analyze various pre-transplantation variable, including donor type, for correlation to outcomes
transplantationcyclophosphamideperform allogeneic HCT for patients with AML in CR1; then analyze various pre-transplantation variable, including donor type, for correlation to outcomes
transplantationmethotrexateperform allogeneic HCT for patients with AML in CR1; then analyze various pre-transplantation variable, including donor type, for correlation to outcomes
Primary Outcome Measures
NameTimeMethod
Efficacy of the treatment measured in terms of frequency of relapse and duration of remissionup to 2 years after transplantation

duration of CR, leukemia recurrence

Secondary Outcome Measures
NameTimeMethod
Engraftmentup to 35 days after transplantation

achievement of neutrophil count over 500/ul

Acute and chronic graft-versus-host diseaseup to 100 days for acute GVHD and up to 2 years for chronic GVHD
Treatment-related mortalityup to 2 years after transplantation
Leukemia-free survival and overall survivalup to 2 years after transplantation

Trial Locations

Locations (2)

Inje University - Haeundae Paik Hospital

🇰🇷

Busan, Korea, Republic of

Asan Medical Center - University of Ulsan College of Medicine

🇰🇷

Seoul, Korea, Republic of

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