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

November 8, 2012 updated by: Morton Cowan, University of California, San Francisco

Bone Marrow Stem Cell Transplantation for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myeloid Leukemia in 1Remission

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94115
        • UCSF Comprehensive Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS:

  • Diagnosis of one of the following hematopoietic disorders:

    • Severe aplastic anemia with marrow aplasia (i.e., absolute neutrophil count < 500/mm^3, platelet and/or red blood cell transfusion dependent), meeting 1 of the following criteria:

      • Closely matched related donor
      • Unresponsive to immunosuppressive therapy within 3 months after follow-up AND alternative matched unrelated donor available

    • Congenital marrow failure syndrome, including any of the following:

      • Primary red blood cell aplasia (Diamond-Blackfan syndrome)
      • Congenital neutropenia (Kostmann's syndrome)
      • Amegakaryocytic thrombocytopenia

    • Hemoglobinopathy including any of the following:

      • β-thalassemia major
      • Sickle cell anemia

    • Severe immunodeficiency disease including any of the following:

      • Chediak-Higashi disease
      • Wiskott-Aldrich syndrome
      • Combined immunodeficiency disease (Nezelof's)
      • Hyperimmunoglobulin M syndrome
      • Bare lymphocyte syndrome
    • Other stem cell defects (e.g., osteopetrosis)

    • Chronic myelogenous leukemia in first chronic phase

      • Not eligible for other ongoing phase II/III studies

    • Acute myeloid leukemia in first remission

      • Not eligible for other ongoing phase II/III studies
    • Inborn errors of metabolism
  • No severe combined immunodeficiency disorder

  • Available donor, meeting 1 of the following criteria:

    • Related donor matched by high resolution DNA typing at both HLA Drβ1 alleles and ≤ 1 mismatch at the 4 HLA-A and -B alleles

    • Unrelated donor, meeting one of the following criteria:

      • Bone marrow matched by high resolution DNA typing at both HLA Drβ1 alleles and ≤ 1 mismatch by high resolution DNA typing at the 4 HLA-A and -B alleles
      • Umbilical cord blood matched at 4/6 HLA-A, -B, and Drβ1 alleles by high resolution typing with ≥ 1 Drβ1 match and ≥ 3 X 10^7 cells/kg body weight of recipient

PATIENT CHARACTERISTICS:

  • See Disease Characteristics
  • No active bacterial, viral, or fungal infection
  • Cardiac shortening fraction ≥ 27%
  • Creatinine clearance ≥ 60 mL/min
  • DLCO ≥ 60% of predicted (corrected for anemia/lung volume)

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

Outcome Measure
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

National Cancer Institute (NCI)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2000

Primary Completion (Actual)

July 1, 2004

Study Completion (Actual)

July 1, 2004

Study Registration Dates

First Submitted

March 21, 2006

First Submitted That Met QC Criteria

March 21, 2006

First Posted (Estimate)

March 22, 2006

Study Record Updates

Last Update Posted (Estimate)

November 12, 2012

Last Update Submitted That Met QC Criteria

November 8, 2012

Last Verified

November 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000462443
  • UCSF-01152
  • UCSF-H411-17802-06

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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