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

July 16, 2012 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 ADULT PATIENTS WITH HEMATOLOGIC MALIGNANCIES AND MYELODYSPLASTIC 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 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 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 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

PATIENT CHARACTERISTICS:

Karnofsky performance status 70-100%
Bilirubin < 2.0 mg/dL
Creatinine < 2.0 mg/dL
AST < 3 times upper limit of normal
Ejection fraction > 40% by MUGA

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
tumor response Time Frame: about 4-8 weeks after transplantation	leukemia CR, CR duration	about 4-8 weeks after transplantation

Secondary Outcome Measures

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

Collaborators and Investigators

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

Sponsor

Asan Medical Center

Collaborators

Pusan National University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Lee KH, Lee JH, Lee JH, Kim DY, Seol M, Lee YS, Kang YA, Jeon M, Hwang HJ, Jung AR, Kim SH, Yun SC, Shin HJ. Reduced-intensity conditioning therapy with busulfan, fludarabine, and antithymocyte globulin for HLA-haploidentical hematopoietic cell transplantation in acute leukemia and myelodysplastic syndrome. Blood. 2011 Sep 1;118(9):2609-17. doi: 10.1182/blood-2011-02-339838. Epub 2011 Jun 28.

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, 2009

Study Completion (Actual)

May 1, 2011

Study Registration Dates

First Submitted

August 8, 2008

First Submitted That Met QC Criteria