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 - Full Text View

Sponsors and Collaborators:	UCSF Helen Diller Family Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00305708

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 I Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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:

MedlinePlus related topics: Anemia Bone Marrow Diseases Bone Marrow Transplantation Cancer Leukemia, Childhood Radiation Therapy

Drug Information available for: Busulfan Fludarabine Fludarabine monophosphate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

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

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

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

UCSF Helen Diller Family Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Morton J. Cowan, MD

UCSF Helen Diller Family Comprehensive Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000462443, UCSF-01152, UCSF-H411-17802-06
Study First Received:	March 21, 2006
Last Updated:	May 9, 2009
ClinicalTrials.gov Identifier:	NCT00305708 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Antimetabolites
Diamond-Blackfan Anemia
Immunologic Factors
Aplastic Anemia
Leukocyte Disorders
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid, Acute
Granulocytopenia
Fanconi's Anemia
Red-Cell Aplasia, Pure
Leukemia
Severe Congenital Neutropenia
Aase Syndrome
Acute Myelocytic Leukemia
Thrombocytopenia

Anemia, Aplastic
Anemia, Diamond-Blackfan
Alkylating Agents
Metabolic Disorder
Metabolic Diseases
Hematologic Diseases
Fanconi Anemia
Blood Platelet Disorders
Anemia
Myeloproliferative Disorders
Agranulocytosis
Congenital Amegakaryocytic Thrombocytopenia
Fludarabine monophosphate
Leukemia, Myeloid
Immunosuppressive Agents

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
DNA Repair-Deficiency Disorders
Leukocyte Disorders
Leukemia, Myeloid, Acute
Red-Cell Aplasia, Pure
Leukemia
Thrombocytopenia
Therapeutic Uses
Anemia, Aplastic
Anemia, Diamond-Blackfan

Alkylating Agents
Metabolic Diseases
Neoplasms by Histologic Type
Hematologic Diseases
Fanconi Anemia
Blood Platelet Disorders
Anemia
Myeloproliferative Disorders
Agranulocytosis
Fludarabine monophosphate
Leukemia, Myeloid
Immunosuppressive Agents
Pharmacologic Actions
Antilymphocyte Serum
Neutropenia

ClinicalTrials.gov processed this record on August 24, 2009