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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Morton Cowan, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00305708
First received: March 21, 2006
Last updated: November 8, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Congenital Amegakaryocytic Thrombocytopenia
Diamond-blackfan Anemia
Fanconi Anemia
Leukemia
Severe Congenital Neutropenia
Thrombocytopenia
Biological: anti-thymocyte globulin
Drug: busulfan
Drug: fludarabine phosphate
Procedure: allogeneic bone marrow transplantation
Procedure: peripheral blood stem cell transplantation
Procedure: umbilical cord blood transplantation
Radiation: radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: Bone Marrow Stem Cell Transplantation for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myeloid Leukemia in 1Remission

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Graft rejection measured by ANC < 500 with no evidence of donor cells in blood or marrow from transplantation to week 4 post transplantation [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity grades 3 or 4 assessed from conditioning through 1 year post transplantation [ Designated as safety issue: Yes ]
  • Engraftment at 1, 3, 6, 9, and 12 months post transplantation [ Designated as safety issue: No ]
  • Mixed chimerism at 1, 3, 6, 9, and 12 months post transplantation [ Designated as safety issue: No ]
  • Survival measured from the day of first dose of conditioning [ Designated as safety issue: No ]
  • Disease-free survival measured from the day of first dose of conditioning [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: August 2000
Study Completion Date: July 2004
Primary Completion Date: July 2004 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00305708

Locations
United States, California
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
Sponsors and Collaborators
University of California, San Francisco
Investigators
Study Chair: Morton J. Cowan, MD University of California, San Francisco
  More Information

Additional Information:
No publications provided

Responsible Party: Morton Cowan, Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00305708     History of Changes
Other Study ID Numbers: CDR0000462443, UCSF-01152, UCSF-H411-17802-06
Study First Received: March 21, 2006
Last Updated: November 8, 2012
Health Authority: United States: Federal Government

Keywords provided by University of California, San Francisco:
thrombocytopenia
childhood acute myeloid leukemia in remission
childhood chronic myelogenous leukemia
Diamond-Blackfan anemia
congenital amegakaryocytic thrombocytopenia
Fanconi anemia
severe congenital neutropenia
chronic phase chronic myelogenous leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Anemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia
Neutropenia
Thrombocytopenia
Fanconi Anemia
Fanconi Syndrome
Anemia, Diamond-Blackfan
Neoplasms by Histologic Type
Neoplasms
Hematologic Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Agranulocytosis
Leukopenia
Leukocyte Disorders
Blood Platelet Disorders
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases
Kidney Diseases
Urologic Diseases
Renal Tubular Transport, Inborn Errors
Metabolism, Inborn Errors
Red-Cell Aplasia, Pure
Fludarabine

ClinicalTrials.gov processed this record on October 01, 2014