Official Title: “Allogeneic Hematopoietic Cell Transplantation for Patients With Acute Myelogenous Leukemia in Remission Using HLA-Matched Sibling Donors, HLA-Matched Unrelated Donors, or HLA-Mismatched Familial Donors - A Phase 2 Study”

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.

Study Type: Interventional

Study Design: Treatment, Open Label

Study Primary Completion Date: December 2013

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.

Intervention(s) in this Clinical Trial

• Biological: anti-thymocyte globulin
• Drug: busulfan
• Drug: cyclophosphamide
• Drug: cyclosporine
• Drug: fludarabine phosphate
• Drug: leucovorin calcium
• Drug: methotrexate
• Drug: methylprednisolone
• Procedure: allogeneic bone marrow transplantation
• Procedure: allogeneic hematopoietic stem cell transplantation
• Procedure: peripheral blood stem cell transplantation

Primary Measures

• Efficacy of the treatment measured in terms of frequency of relapse and duration of remission
  • Safety Issue?: No

Secondary Measures

• Engraftment
  • Safety Issue?: No
• Donor chimerism at 2 and 4 weeks after HSCT
  • Safety Issue?: No
• Secondary graft failure
  • Safety Issue?: No
• Acute and chronic graft-versus-host disease
  • Safety Issue?: Yes
• Treatment-related mortality
  • Safety Issue?: No
• Leukemia-free survival and overall survival
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Diagnosis of acute myeloid leukemia (AML) meeting 1 of the following criteria:
• Achieved complete response (CR1) after induction chemotherapy
• Recurrent AML that went into second CR (CR2) after salvage chemotherapy, except those who have undergone prior allogeneic HSCT
• No acute promyelocytic leukemia or acute myeloid leukemia with chromosomal changes t(8;21), inv 16, or t(15;17)
• Must have a donor available meeting one of the following criteria:
• HLA-matched sibling of 65 years or younger
• 6/6 HLA-matched unrelated donor (younger than 55 years) for antigen A, B, and DR
• HLA-mismatched family member (offspring, parents, haploidentical sibling)

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• Bilirubin < 2.0 mg/dL
• AST < 3 times the upper limit of normal
• Creatinine < 2.0 mg/dL
• Ejection fraction > 40% on MUGA scan
• Negative pregnancy test

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 15 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Asan Medical Center

Overall Clinical Trial Officials and Contacts

Kyoo H. Lee, MD Principal Investigator Asan Medical Center  

Information obtained from ClinicalTrials.gov on February 08, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01020734

Study ID Number: CDR0000659891

ClinicalTrials.gov Identifier: NCT01020734

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database