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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00731328
• Other study ID #: CDR0000600351
• Secondary ID: AMC-UUCM-2008-00
• Status: Completed
• Phase: Phase 2
• First received: August 8, 2008
• Last updated: December 29, 2015
• Start date: April 2008
• Est. completion date: December 2013

Study information

• Verified date: December 2015
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 75 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hemoglobinuria
• Hemoglobinuria, Paroxysmal
• Leukemia
• Myelodysplastic Syndromes
• Nonmalignant Neoplasm
• Pancytopenia
• Paroxysmal Nocturnal Hemoglobinuria
• Preleukemia
• Syndrome

Intervention

Procedure:
• nonmyeloablative allogeneic hematopoietic stem cell transplantation
infusion of mobilized donor hematopoietic progenitor cells

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center - University of Ulsan College of Medicine	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Donor cell engraftment	neutrophil count over 500/ul	10-35 days after transplantation	No
Secondary	Regimen-related toxicities as assessed by NCI's Common Toxicity Criteria	various toxicities of treatment	0-60 months after transplantation	Yes
Secondary	Acute and chronic GVHD	ocurrence of acute or chronic GVHD after transplantation	15-100 days; 100 days to 4 years	Yes
Secondary	overall survival	patients surviving after transplantaion	0-60 months	Yes
Secondary	event-free survival	patients undergoing transplantation and maintaining donor hematopoiesis	0-60 months after transplatation	Yes