Back to resultsBusulfan, 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
Primary Purpose
Congenital Amegakaryocytic Thrombocytopenia, Diamond-blackfan Anemia, Fanconi Anemia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
anti-thymocyte globulin
busulfan
fludarabine phosphate
allogeneic bone marrow transplantation
peripheral blood stem cell transplantation
umbilical cord blood transplantation
radiation therapy
Sponsored by
About this trial
This is an interventional treatment trial for Congenital Amegakaryocytic Thrombocytopenia focused on measuring 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
Eligibility 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
Sites / Locations
- UCSF Comprehensive Cancer Center
Outcomes
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
Secondary Outcome Measures
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
Full Information
NCT ID
NCT00305708
First Posted
March 21, 2006
Last Updated
November 8, 2012
Sponsor
University of California, San Francisco
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT00305708
Brief Title
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
Official Title
Bone Marrow Stem Cell Transplantation for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myeloid Leukemia in 1Remission
Study Type
Interventional
2. Study Status
Record Verification Date
November 2012
Overall Recruitment Status
Completed
Study Start Date
August 2000 (undefined)
Primary Completion Date
July 2004 (Actual)
Study Completion Date
July 2004 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of California, San Francisco
Collaborators
National Cancer Institute (NCI)
4. Oversight
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Congenital Amegakaryocytic Thrombocytopenia, Diamond-blackfan Anemia, Fanconi Anemia, Leukemia, Severe Congenital Neutropenia, Thrombocytopenia
Keywords
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Masking
None (Open Label)
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Biological
Intervention Name(s)
anti-thymocyte globulin
Intervention Type
Drug
Intervention Name(s)
busulfan
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Intervention Type
Procedure
Intervention Name(s)
peripheral blood stem cell transplantation
Intervention Type
Procedure
Intervention Name(s)
umbilical cord blood transplantation
Intervention Type
Radiation
Intervention Name(s)
radiation therapy
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Toxicity grades 3 or 4 assessed from conditioning through 1 year post transplantation
Title
Engraftment at 1, 3, 6, 9, and 12 months post transplantation
Title
Mixed chimerism at 1, 3, 6, 9, and 12 months post transplantation
Title
Survival measured from the day of first dose of conditioning
Title
Disease-free survival measured from the day of first dose of conditioning
10. Eligibility
Sex
All
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Morton J. Cowan, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Study Chair
Facility Information:
Facility Name
UCSF Comprehensive Cancer Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
12. IPD Sharing Statement
Learn more about this trial
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
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