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


Phase 1/Phase 2
N/A
17 Years
Not Enrolling
Both
Congenital Amegakaryocytic Thrombocytopenia, Diamond-blackfan Anemia, Fanconi Anemia, Leukemia, Severe Congenital Neutropenia, Thrombocytopenia

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

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

Safety Issue:

No

Principal Investigator

Morton J. Cowan, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Francisco

Authority:

United States: Federal Government

Study ID:

CDR0000462443

NCT ID:

NCT00305708

Start Date:

August 2000

Completion Date:

July 2004

Related Keywords:

  • Congenital Amegakaryocytic Thrombocytopenia
  • Diamond-Blackfan Anemia
  • Fanconi Anemia
  • Leukemia
  • Severe Congenital Neutropenia
  • Thrombocytopenia
  • 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
  • Anemia
  • Fanconi Anemia
  • Fanconi Syndrome
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Neutropenia
  • Thrombocytopenia
  • Anemia, Diamond-Blackfan

Name

Location

UCSF Comprehensive Cancer CenterSan Francisco, California  94115