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

December 29, 2015 updated by: Kyoo-Hyung Lee, Asan Medical Center

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation

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.

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Korea, Republic of
- - Seoul, Korea, Republic of, 138-736
    - Asan Medical Center - University of Ulsan College of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 75 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: Treatment
Allocation: N/A
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Donor cell engraftment Time Frame: 10-35 days after transplantation	neutrophil count over 500/ul	10-35 days after transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regimen-related toxicities as assessed by NCI's Common Toxicity Criteria Time Frame: 0-60 months after transplantation	various toxicities of treatment	0-60 months after transplantation
Acute and chronic GVHD Time Frame: 15-100 days; 100 days to 4 years	ocurrence of acute or chronic GVHD after transplantation	15-100 days; 100 days to 4 years
overall survival Time Frame: 0-60 months	patients surviving after transplantaion	0-60 months
event-free survival Time Frame: 0-60 months after transplatation	patients undergoing transplantation and maintaining donor hematopoiesis	0-60 months after transplatation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Asan Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2008

Primary Completion (Actual)

December 1, 2013

Study Completion (Actual)

December 1, 2013

Study Registration Dates

First Submitted

August 8, 2008

First Submitted That Met QC Criteria