Donor Stem Cell Transplant After Busulfan, Fludarabine, and Antithymocyte Globulin in Treating Patients With Hematological Cancer

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00627666
First received: February 29, 2008
Last updated: March 25, 2013
Last verified: July 2009

February 29, 2008
March 25, 2013
January 2003
June 2010   (final data collection date for primary outcome measure)
  • Treatment-related mortality [ Designated as safety issue: Yes ]
  • Engraftment [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00627666 on ClinicalTrials.gov Archive Site
  • Regimen-related toxicities [ Designated as safety issue: Yes ]
  • Graft-versus-host-disease [ Designated as safety issue: Yes ]
  • Relapse [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Failure-free survival [ Designated as safety issue: No ]
  • 100-day transplant-related mortality [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Donor Stem Cell Transplant After Busulfan, Fludarabine, and Antithymocyte Globulin in Treating Patients With Hematological Cancer
Unrelated Donor Hematopoietic Stem Cell Transplantation After Nonmyeloablative Conditioning For Patients With Hematological Malignancies

RATIONALE: Giving chemotherapy before a donor bone marrow stem cell transplant helps stop the growth of cancer cells. Chemotherapy and antithymocyte globulin 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 cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and methotrexate after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving donor stem cell transplant together with busulfan, fludarabine, and antithymocyte globulin works in treating patients with hematological cancer.

OBJECTIVES:

  • To investigate whether unrelated donor hematopoietic stem cell transplantation using a nonmyeloablative conditioning regimen comprising busulfan, fludarabine phosphate, and anti-thymocyte globulin can reduce treatment-related mortality in patients with hematologic malignancies.
  • To investigate whether this regimen can be sufficiently immunosuppressive to enable engraftment of HLA-matched unrelated hematopoietic stem cells.

OUTLINE: This is a multicenter study.

Prior to receiving the conditioning chemotherapy regimen, all patients with acute leukemia, chronic myelogenous leukemia (CML), and high-risk myelodysplastic syndromes (chronic myelomonocytic leukemia, atypical CML, and refractory anemia with excess blasts) receive one dose of intrathecal (IT) methotrexate. These patients also receive leucovorin calcium IV or orally 4 hours after IT methotrexate and every 6 hours for a total of 8 doses.

  • Nonmyeloablative conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -2, busulfan IV over 3 hours on days -7 to -6, anti-thymocyte globulin IV over 4 hours on days -4 to -2.
  • Allogeneic bone marrow stem cell transplantation (SCT): Patients undergo allogeneic bone marrow SCT on day 0.
  • Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine (CSA) IV over 2-4 hours every 12 hours starting on day -1 and continuing until day 180 (CSA can be given orally every 12 hours once oral medication can be tolerated) and methotrexate IV on days 1, 3 , 6 , and 11.

Once blood counts recover, patients with acute leukemia or CML in blast crisis resume IT methotrexate once every 2 weeks for a total of 3 doses. Patients also receive leucovorin calcium IV or orally 4 hours after IT methotrexate and then every 6 hours for a total of 8 doses.

Patients are followed for at least 10 years after SCT.

Interventional
Phase 2
Masking: Open Label
Primary Purpose: Treatment
  • Leukemia
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasms
  • Biological: anti-thymocyte globulin
  • Drug: busulfan
  • Drug: fludarabine phosphate
  • Drug: leucovorin calcium
  • Drug: methotrexate
  • Procedure: allogeneic bone marrow transplantation
  • Procedure: allogeneic hematopoietic stem cell transplantation
  • Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Not Provided
Lee KH, Choi SJ, Lee JH, Lee JH, Kim DY, Seol M, Lee YS, Kang YA, Jeon M, Yun SC, Joo YD, Lee WS, Kang MJ, Kim H, Park JH, Bae SH, Ryoo HM, Kim MK, Hyun MS. Clinical effect of reduced-intensity conditioning regimen containing antithymocyte globulin for hematopoietic cell transplantation from unrelated-donors. Am J Hematol. 2011 May;86(5):399-405.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
52
June 2010
June 2010   (final data collection date for primary outcome measure)

DISEASE CHARACTERISTICS:

  • Diagnosis of any 1 of the following:

    • Acute leukemia
    • Chronic myelogenous leukemia
    • Myelodysplastic syndromes
  • Must have an unrelated donor available who is matched for HLA-A and -B by serology and for DRB1 by molecular typing

PATIENT CHARACTERISTICS:

  • Karnofsky performance status 70-100%
  • Bilirubin < 3.0 mg/dL
  • Creatinine < 2.0 mg/dL
  • AST and ALT < 3 times the upper limit of normal
  • Not pregnant or nursing
  • Ejection fraction ≥ 45% by MUGA scan or ECHO
  • No major illness or organ failure
  • No severe psychiatric disorder or mental deficiency that makes compliance with the treatment unlikely and informed consent impossible

PRIOR CONCURRENT THERAPY:

  • Not specified
Both
15 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Korea, Republic of
 
NCT00627666
CDR0000583220, AMC-UUCM-2003-0207
Not Provided
Not Provided
Asan Medical Center
Not Provided
Study Chair: Kyoo H. Lee, MD Asan Medical Center
National Cancer Institute (NCI)
July 2009

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