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Donor Stem Cell Transplant After Busulfan, Fludarabine, Methylprednisolone, and Antithymocyte Globulin in Treating Patients With Bone Marrow Failure Syndrome

This study is currently recruiting participants.
Verified July 2012 by Asan Medical Center
Sponsor:
Information provided by (Responsible Party):
Kyoo-Hyung Lee, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT00731328
First received: August 8, 2008
Last updated: July 15, 2012
Last verified: July 2012
History of Changes
  Purpose

RATIONALE: Giving low doses of chemotherapy and antithymocyte globulin before a donor stem cell transplant helps stop the growth of abnormal cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining abnormal cells (graft-versus-tumor effect).

PURPOSE: This phase II trial is studying how well a donor stem cell transplant works after busulfan, fludarabine, methylprednisolone, and antithymocyte globulin in treating patients with bone marrow failure syndrome.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Nonmalignant Neoplasm
Paroxysmal Nocturnal Hemoglobinuria
 Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: HLA-HAPLOIDENTICAL FAMILIAL DONOR HEMATOPOIETIC CELL TRANSPLANTATION AFTER REDUCED INTENSITY CONDITIONING OF BUSULFAN, FLUDARABINE, AND ANTI-THYMOCYTE GLOBULIN FOR PATIENTS WITH BONE MARROW FAILURE SYNDROME - A PHASE 2 STUDY

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • Donor cell engraftment [ Time Frame: 10-35 days after transplantation ] [ Designated as safety issue: No ]
    neutrophil count over 500/ul


Secondary Outcome Measures:
  • Regimen-related toxicities as assessed by NCI's Common Toxicity Criteria [ Time Frame: 0-60 months after transplantation ] [ Designated as safety issue: Yes ]
    various toxicities of treatment

  • Acute and chronic GVHD [ Time Frame: 15-100 days; 100 days to 4 years ] [ Designated as safety issue: Yes ]
    ocurrence of acute or chronic GVHD after transplantation

  • overall survival [ Time Frame: 0-60 months ] [ Designated as safety issue: Yes ]
    patients surviving after transplantaion

  • event-free survival [ Time Frame: 0-60 months after transplatation ] [ Designated as safety issue: Yes ]
    patients undergoing transplantation and maintaining donor hematopoiesis


Estimated Enrollment: 50
Study Start Date: April 2008
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
    infusion of mobilized donor hematopoietic progenitor cells
Detailed Description:

OBJECTIVES:

  • To evaluate the efficacy of HLA-haploidentical familial donor hematopoietic stem cell transplantation after reduced-intensity conditioning regimen comprising busulfan, fludarabine phosphate, and anti-thymocyte globulin in patients with bone marrow failure syndromes.

OUTLINE:

  • Reduced-intensity conditioning regimen: Patients receive busulfan IV daily on days -7 and -6, fludarabine phosphate IV over 30 minutes on days -7 to -2, anti-thymocyte globulin (ATG) IV over 4 hours on days -4 to -1, and methylprednisolone IV over 30 minutes starting 30 minutes before ATG on days -4 to -1.
  • HLA-haploidentical donor hematopoietic stem cell transplantation: Patients receive donor hematopoietic stem cells via Hickman catheter over 1 hour on days 0 or 1.
  • Graft-versus-host-disease prophylaxis (GVHD): Patients receive cyclosporine IV over 2-4 hours every 12 hours starting on day -1 (cyclosporine can be given orally once oral medication can be tolerated) and methotrexate IV on days 2, 4 , 7, and 12. In the absence of GVHD, cyclosporine is tapered starting between days 30 to 60.

After completion of study treatment, patients are followed periodically for 1 year.

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of any of the following bone marrow failure syndromes:

    • Severe aplastic anemia, meeting 1 of the following criteria:

      • Not responsive to immunosuppressive therapy
      • With recurrent cytopenia after immunosuppressive therapy or allogeneic hematopoietic cell transplantation

    • Low-risk myelodysplastic syndrome, including any of the following:

      • Refractory anemia
      • Refractory anemia with ringed sideroblasts
      • Refractory cytopenia with multi-lineage dysplasia

    • Paroxysmal nocturnal hemoglobinuria, meeting 1 of the following criteria:

      • With thrombotic episodes
      • With severe cytopenia

  • No willing, suitable HLA-compatible donor in family or in donor registries

    • Related donor with HLA-haploidentical mismatch at three or less of 6 loci
    • Patients with very severe neutropenia (< 200/μL) or febrile episodes, who feel urgent need for allogeneic hematopoietic cell transplantation, are eligible without a search for HLA-matched unrelated donors

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 70-100%
  • Bilirubin < 2.0 mg/dL
  • AST < 3 times upper limit of normal
  • Creatinine < 2.0 mg/dL
  • Ejection fraction > 40% by MUGA scan

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00731328

Locations
Korea, Republic of
Asan Medical Center - University of Ulsan College of Medicine Recruiting
Seoul, Korea, Republic of, 138-736
Contact: Kyoo H. Lee, MD     82-2-2224-3210     khlee2@amc.seoul.kr    
Sponsors and Collaborators
Asan Medical Center
Investigators
Principal Investigator: Kyoo H. Lee, MD Asan Medical 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

Responsible Party: Kyoo-Hyung Lee, Professor of Internal Medicine, Asan Medical Center
ClinicalTrials.gov Identifier: NCT00731328     History of Changes
Other Study ID Numbers: CDR0000600351, AMC-UUCM-2008-0038
Study First Received: August 8, 2008
Last Updated: July 15, 2012
Health Authority: Korea: Food and Drug Administration

Keywords provided by Asan Medical Center:
refractory anemia
refractory anemia with ringed sideroblasts
refractory cytopenia with multilineage dysplasia
childhood myelodysplastic syndromes
de novo myelodysplastic syndromes
 previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
aplastic anemia
paroxysmal nocturnal hemoglobinuria

Additional relevant MeSH terms:
Neoplasms
Hemoglobinuria
Leukemia
Hemoglobinuria, Paroxysmal
Myelodysplastic Syndromes
Preleukemia
Pancytopenia
Proteinuria
Urination Disorders
Urologic Diseases
Urological Manifestations
Signs and Symptoms
Neoplasms by Histologic Type
Anemia, Hemolytic
Anemia
 Hematologic Diseases
Bone Marrow Diseases
Precancerous Conditions
Antilymphocyte Serum
Busulfan
Fludarabine
Methylprednisolone
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 16, 2013