Busulfan, Antithymocyte Globulin, and Fludarabine Followed By a Donor Stem Cell Transplant in Treating Young Patients With Blood Disorders, Bone Marrow Disorders, Chronic Myelogenous Leukemia in First Chronic Phase, or Acute Myeloid Leukemia in First Remission

Phase 1

Completed

• Conditions: Congenital Amegakaryocytic Thrombocytopenia; Diamond-blackfan Anemia; Fanconi Anemia; Leukemia; Severe Congenital Neutropenia; Thrombocytopenia

• Registration Number: NCT00305708
• Lead Sponsor: University of California, San Francisco

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as busulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. A donor peripheral blood, bone marrow , or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving antithymocyte globulin before the transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the side effects of busulfan, antithymocyte globulin, and fludarabine when given together with a donor stem cell transplant in treating young patients with blood disorders, bone marrow disorders, chronic myelogenous leukemia in first chronic phase, or acute myeloid leukemia in first remission.

Detailed Description

OBJECTIVES:

Primary

* Determine the efficacy, in terms of graft rejection at 4 weeks, of a conditioning regimen comprising busulfan, anti-thymocyte globulin, and fludarabine followed by donor stem cell transplantation (SCT) in children with stem cell defects, marrow failure syndromes, chronic myelogenous leukemia in first chronic phase, or acute myeloid leukemia in first remission.

* Determine the pharmacokinetics of busulfan in children undergoing donor SCT.

Secondary

* Determine the toxicity of this regimen in these patients.

* Determine engraftment at 3, 6, 9, and 12 months and mixed chimerism in patients treated with this regimen.

* Determine overall and disease-free survival of patients treated with this regimen.

OUTLINE: Patients receive one of the following cytoreductive regimens:

* Regimen 1 (patients with an HLA genotypic matched sibling donor): Patients receive busulfan IV over 2 hours every 6 hours on days -9 to -6, fludarabine IV on days -5 to -2, and anti-thymocyte globulin (ATG) IV over 10 hours on days -3 to -1.

* Regimen 2 (patients with an HLA closely matched related \[not genotypic\] or unrelated donor): Patients receive busulfan and fludarabine as in regimen 1, and ATG IV over 10 hours on days -4 to -1.

* Regimen 3 (patients with Fanconi's anemia or severe aplastic anemia with genotypic matched sibling donor): Patients receive fludarabine as in regimen 1 and ATG as in regimen 2.

* Regimen 4 (patients with Fanconi's anemia who have a closely matched related \[not genotypic\] or unrelated donor): Patients undergo thoracoabdominal irradiation on day -6 and receive fludarabine as in regimen 1 and ATG as in regimen 2.

All patients undergo allogeneic bone marrow, umbilical cord blood, or peripheral blood stem cell transplantation on day 0.

After the completion of study treatment, patients are followed periodically for 20 years.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Study Timeline

• Study Start: 2000-08
• Primary Completion: 2004-07
• Study Completion: 2004-07
• Study First Submitted: 2006-03-21
• Study First Submitted QC: 2006-03-21
• Study First Posted: 2006-03-22
• Status Verified: 2012-11
• Last Update Submitted: 2012-11-08
• Last Update Posted: 2012-11-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Graft rejection measured by ANC < 500 with no evidence of donor cells in blood or marrow from transplantation to week 4 post transplantation

Secondary Outcome Measures

Name	Time	Method
Toxicity grades 3 or 4 assessed from conditioning through 1 year post transplantation
Engraftment at 1, 3, 6, 9, and 12 months post transplantation
Mixed chimerism at 1, 3, 6, 9, and 12 months post transplantation
Survival measured from the day of first dose of conditioning
Disease-free survival measured from the day of first dose of conditioning

Trial Locations

Locations (1)

UCSF Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States