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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

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

NCT ID

NCT00731328

First Posted

August 8, 2008

Last Updated

December 29, 2015

Sponsor

Asan Medical Center

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

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

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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