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

This study has been completed.
Sponsor:
Collaborator:
Pusan National University Hospital
Information provided by (Responsible Party):
Kyoo-Hyung Lee, Asan Medical Center
ClinicalTrials.gov Identifier:
NCT00732316
First received: August 8, 2008
Last updated: July 16, 2012
Last verified: July 2012
  Purpose

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 Intervention Phase
Leukemia
Myelodysplastic Syndromes
Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Asan Medical Center:

Primary Outcome Measures:
  • tumor response [ Time Frame: about 4-8 weeks after transplantation ] [ Designated as safety issue: No ]
    leukemia CR, CR duration


Secondary Outcome Measures:
  • Donor cell engraftment (neutrophil, platelet, and red blood cells) [ Time Frame: 10-35 days after transplantation ] [ Designated as safety issue: No ]
    neutrophi count over 500/ul

  • Acute and chronic graft-versus-host disease [ Time Frame: 15-100 days; 100 days to 4 years ] [ Designated as safety issue: No ]
    ocurrence of acute or chronic GVHD


Enrollment: 54
Study Start Date: April 2008
Study Completion Date: May 2011
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
    administration of conditioning therapy including immunosuppressive agents plus alkylating agents and infusing hematopoietic progenitor cells collected from the donor
    Procedure: peripheral blood stem cell transplantation
    infusion of donor hematopoietic cells collected by leukapheresis after mobilization with growth factor
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.

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00732316

Locations
Korea, Republic of
Asan Medical Center - University of Ulsan College of Medicine
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Asan Medical Center
Pusan National University Hospital
Investigators
Principal Investigator: Kyoo H. Lee, MD Asan Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: Kyoo-Hyung Lee, Professor of Internal Medicine, Asan Medical Center
ClinicalTrials.gov Identifier: NCT00732316     History of Changes
Other Study ID Numbers: CDR0000600347, AMC-UUCM-2008-0037
Study First Received: August 8, 2008
Last Updated: July 16, 2012
Health Authority: Korea: Food and Drug Administration

Keywords provided by Asan Medical Center:
accelerated phase chronic myelogenous leukemia
adult acute lymphoblastic leukemia in remission
adult acute myeloid leukemia in remission
acute undifferentiated leukemia
blastic phase chronic myelogenous leukemia
childhood acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
childhood chronic myelogenous leukemia
childhood myelodysplastic syndromes
chronic phase chronic myelogenous leukemia
chronic myelomonocytic leukemia
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
recurrent childhood acute lymphoblastic leukemia
recurrent childhood acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
relapsing chronic myelogenous leukemia
secondary myelodysplastic syndromes

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Leukemia
Syndrome
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Neoplasms by Histologic Type
Disease
Pathologic Processes
Fludarabine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014