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

Leukemia Clinical Trial

Official title:

Unrelated Donor Hematopoietic Stem Cell Transplantation After Nonmyeloablative Conditioning For Patients With Hematological Malignancies

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00627666
• Other study ID #: CDR0000583220
• Secondary ID: AMC-UUCM-2003-02
• Status: Completed
• Phase: Phase 2
• First received: February 29, 2008
• Last updated: March 25, 2013
• Start date: January 2003
• Est. completion date: June 2010

Study information

• Verified date: July 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 65 Years

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Neoplasms
• Myeloproliferative Disorders
• Preleukemia

Intervention

Biological:
• anti-thymocyte globulin

Drug:
• busulfan

• fludarabine phosphate

• leucovorin calcium

• methotrexate

Procedure:
• allogeneic bone marrow transplantation

• allogeneic hematopoietic stem cell transplantation

• nonmyeloablative allogeneic hematopoietic stem cell transplantation

Locations

Country	Name	City	State
Korea, Republic of	Asan Medical Center - University of Ulsan College of Medicine	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Asan Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (1)

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 he — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment-related mortality			Yes
Primary	Engraftment			No
Secondary	Regimen-related toxicities			Yes
Secondary	Graft-versus-host-disease			Yes
Secondary	Relapse			No
Secondary	Overall survival			No
Secondary	Failure-free survival			No
Secondary	100-day transplant-related mortality			Yes