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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

August 8, 2008
July 16, 2012
April 2008
December 2009   (final data collection date for primary outcome measure)
tumor response [ Time Frame: about 4-8 weeks after transplantation ] [ Designated as safety issue: No ]
leukemia CR, CR duration
  • Response duration [ Designated as safety issue: No ]
  • Disease response rate [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00732316 on ClinicalTrials.gov Archive Site
  • 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
  • Donor cell engraftment (neutrophil, platelet, and red blood cells) [ Designated as safety issue: No ]
  • Complete donor hematopoietic chimerism as assessed by short tandem repeats-PCR [ Designated as safety issue: No ]
  • Regimen-related toxicities [ Designated as safety issue: Yes ]
  • Acute and chronic graft-versus-host disease [ Designated as safety issue: No ]
  • Post-transplant immune reconstitution [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Donor Stem Cell Transplant After Busulfan, Fludarabine, and Antithymocyte Globulin in Treating Patients With Hematologic Cancer or Myelodysplastic Syndrome
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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Leukemia
  • Myelodysplastic Syndromes
  • 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
Not Provided
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
54
May 2011
December 2009   (final data collection date for primary outcome measure)

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
Both
up to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
Korea, Republic of
 
NCT00732316
CDR0000600347, AMC-UUCM-2008-0037
No
Kyoo-Hyung Lee, Asan Medical Center
Asan Medical Center
Pusan National University Hospital
Principal Investigator: Kyoo H. Lee, MD Asan Medical Center
Asan Medical Center
July 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP