Donor Stem Cell Transplant After Busulfan, Fludarabine, and Antithymocyte Globulin in Treating Patients With Hematologic Cancer or Myelodysplastic Syndrome

Sponsor

Asan Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00732316

Collaborator

Pusan National University Hospital (Other)

Enrollment

Location

Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Giving low doses of chemotherapy and antithymocyte globulin before a donor stem cell transplant helps stop the growth of cancer and 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 cancer and abnormal cells (graft-versus-tumor effect).

PURPOSE: This phase II trial is studying how well a donor stem cell transplant works after busulfan, fludarabine, and antithymocyte globulin in treating patients with hematologic cancer or myelodysplastic syndrome.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes	Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation	Phase 2

Detailed Description

OBJECTIVES:

To evaluate the efficacy of HLA-haploidentical familial donor hematopoietic cell transplantation with a reduced-intensity conditioning regimen of busulfan, fludarabine phosphate, and anti-thymocyte globulin in patients with hematologic malignancies or myelodysplastic syndromes.

OUTLINE: Before receiving the reduced-intensity conditioning regimen, patients receive one dose of intrathecal (IT) methotrexate, then leucovorin calcium IV or orally 4 hours after methotrexate and every 6 hours for a total of 8 doses.

Reduced-intensity conditioning regimen: Patients receive busulfan IV over 6 hours 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 on days -4 to -1.
HLA-haploidentical familial donor hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT over 1 hour on days 0 and 1.
Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV* over 2-4 hours every 12 hours on days -1 to 30 followed by a taper until day 60 and methotrexate IV on days 2, 4 , 7, and 12.

NOTE: *Cyclosporine can be given orally once oral medication can be tolerated

CNS prophylaxis: When blood counts recover, patients with acute leukemia or chronic myelogenous leukemia in blastic crisis resume IT methotrexate once every 2 weeks for a total of 4 doses (including the dose given before the conditioning regimen) and leucovorin calcium IV or orally 4 hours after (each dose of methotrexate) and every 6 hours for a total of 8 doses.

After completion of study treatment, patients are followed periodically for up to 3 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

54 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (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 ADULT PATIENTS WITH HEMATOLOGIC MALIGNANCIES AND MYELODYSPLASTIC SYNDROME - A PHASE 2 STUDY

Study Start Date :

Apr 1, 2008

Actual Primary Completion Date :

Dec 1, 2009

Actual Study Completion Date :

May 1, 2011

Outcome Measures

Primary Outcome Measures

tumor response [about 4-8 weeks after transplantation]
leukemia CR, CR duration

Secondary Outcome Measures

Donor cell engraftment (neutrophil, platelet, and red blood cells) [10-35 days after transplantation]
neutrophi count over 500/ul
Acute and chronic graft-versus-host disease [15-100 days; 100 days to 4 years]
ocurrence of acute or chronic GVHD

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following hematological malignancies:
Acute leukemia, including any of the following:
Refractory acute leukemia
Acute leukemia beyond first remission
Acute leukemia in first remission with intermediate to poor prognostic features as suggested by chromosomal findings
Chronic myelogenous leukemia (CML)
Second chronic phase
Accelerated phase
Blastic phase
Myelodysplastic syndrome (MDS)
High-risk MDS (refractory anemia with excess blasts [RAEB], RAEB in transformation, and chronic myelomonocytic leukemia) can be transplanted without prior therapy or after prior therapy failure with hypomethylating agents
Low-risk MDS can be considered for transplantation after prior therapy failure with immunosuppressive or hypomethylating agents
No willing, suitable HLA-matched donor in family or in donor registries
Patients with active hematologic malignancy, who are felt to be in urgent need of allogeneic hematopoietic cell transplantation, can enroll without a search for HLA-matched unrelated donors
Related donor with HLA-haploidentical mismatch at 3 or less of 6 loci available