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

Primary Purpose

Leukemia, Myelodysplastic Syndromes, Nonmalignant Neoplasm

Status
Completed
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
nonmyeloablative allogeneic hematopoietic stem cell transplantation
Sponsored by
Asan Medical Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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

Eligibility Criteria

undefined - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Asan Medical Center - University of Ulsan College of Medicine

Outcomes

Primary Outcome Measures

Donor cell engraftment
neutrophil count over 500/ul

Secondary Outcome Measures

Regimen-related toxicities as assessed by NCI's Common Toxicity Criteria
various toxicities of treatment
Acute and chronic GVHD
ocurrence of acute or chronic GVHD after transplantation
overall survival
patients surviving after transplantaion
event-free survival
patients undergoing transplantation and maintaining donor hematopoiesis

Full Information

First Posted
August 8, 2008
Last Updated
December 29, 2015
Sponsor
Asan Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT00731328
Brief Title
Donor Stem Cell Transplant After Busulfan, Fludarabine, Methylprednisolone, and Antithymocyte Globulin in Treating Patients With Bone Marrow Failure Syndrome
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
Study Type
Interventional

2. Study Status

Record Verification Date
December 2015
Overall Recruitment Status
Completed
Study Start Date
April 2008 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Asan Medical Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myelodysplastic Syndromes, Nonmalignant Neoplasm, Paroxysmal Nocturnal Hemoglobinuria
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Procedure
Intervention Name(s)
nonmyeloablative allogeneic hematopoietic stem cell transplantation
Intervention Description
infusion of mobilized donor hematopoietic progenitor cells
Primary Outcome Measure Information:
Title
Donor cell engraftment
Description
neutrophil count over 500/ul
Time Frame
10-35 days after transplantation
Secondary Outcome Measure Information:
Title
Regimen-related toxicities as assessed by NCI's Common Toxicity Criteria
Description
various toxicities of treatment
Time Frame
0-60 months after transplantation
Title
Acute and chronic GVHD
Description
ocurrence of acute or chronic GVHD after transplantation
Time Frame
15-100 days; 100 days to 4 years
Title
overall survival
Description
patients surviving after transplantaion
Time Frame
0-60 months
Title
event-free survival
Description
patients undergoing transplantation and maintaining donor hematopoiesis
Time Frame
0-60 months after transplatation

10. Eligibility

Sex
All
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kyoo H. Lee, MD
Organizational Affiliation
Asan Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Asan Medical Center - University of Ulsan College of Medicine
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of

12. IPD Sharing Statement

Learn more about this trial

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

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