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

NCT00305708 | Completed Phase 1

• 3 other identifiers: CDR0000462443UCSF-01152UCSF-H411-17802-06
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Graft rejection measured by ANC < 500 with no evidence of donor cells in blood or marrow from transplantation to week 4 post transplantation

Secondary Outcomes (5)

• 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

Interventions

anti-thymocyte globulin BIOLOGICAL

busulfan DRUG

fludarabine phosphate DRUG

allogeneic bone marrow transplantation PROCEDURE

peripheral blood stem cell transplantation PROCEDURE

umbilical cord blood transplantation PROCEDURE

radiation therapy RADIATION

Eligibility Criteria

• Age: Up to 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

UCSF Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

MeSH Terms

Conditions

Congenital amegakaryocytic thrombocytopenia; Anemia, Diamond-Blackfan; Fanconi Anemia; Leukemia; Neutropenia, Severe Congenital, Autosomal Recessive 3; Thrombocytopenia; Leukemia, Myeloid, Chronic-Phase

Interventions

Antilymphocyte Serum; Busulfan; fludarabine phosphate; Peripheral Blood Stem Cell Transplantation; Cord Blood Stem Cell Transplantation; Radiotherapy

Condition Hierarchy (Ancestors)

Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Red-Cell Aplasia, Pure; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Neoplasms by Histologic Type; Neoplasms; Blood Platelet Disorders; Cytopenia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Morton J. Cowan, MD

  University of California, San Francisco

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 21, 2006
• First Posted: March 22, 2006
• Study Start: August 1, 2000
• Primary Completion: July 1, 2004
• Study Completion: July 1, 2004
• Last Updated: November 12, 2012

Record last verified: 2012-11

Locations

US (1)