Fludarabine and Busulfan Followed by Donor Peripheral Stem Cell Transplant and Antithymocyte Globulin, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Cancer

NCT ID: NCT00346359

Last Updated: 2010-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-03-31
• Study Completion Date: 2007-11-30

Brief Summary

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral stem cell transplant helps stop the growth of abnormal and cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining abnormal or 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 antithymocyte globulin, tacrolimus, and methotrexate before or after transplant may stop this from happening.

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

Detailed Description

OBJECTIVES:

Primary

• Determine the incidence and severity of acute graft-versus-host disease (GVHD) in patients with myeloid malignancies treated with conditioning regimen comprising fludarabine phosphate and busulfan followed by allogeneic peripheral blood stem cell transplantation and GVHD prophylaxis comprising antithymocyte globulin, tacrolimus, and methotrexate.
• Determine the incidence of donor engraftment in patients treated with this regimen.

Secondary

• Determine the pharmacokinetics of IV busulfan, including interdose variability and evaluation of a limited sampling strategy, in these patients.
• Determine the pharmacokinetics of antithymocyte globulin in these patients.
• Determine the pharmacokinetics of fludarabine phosphate and its effect on lymphocytes in these patients.
• Determine the incidence of specific toxic effects ≥ grade 3 in patients treated with this regimen.
• Determine the incidence and severity of chronic GVHD in these patients.
• Determine the incidence of nonrelapsing mortality at 100 days and at 1 year after transplantation in these patients.
• Determine the incidence of relapse in these patients.
• Determine relapse-free survival of these patients.
• Determine the incidence of Epstein-Barr virus activation in these patients.

OUTLINE:

• Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and busulfan IV over 3 hours on days -5 to -2. Prior to the conditioning regimen, patients whose cerebrospinal fluid is positive for malignant cells receive intrathecal methotrexate or cranial irradiation for CNS prophylaxis.
• Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients receive filgrastim (G-CSF)-mobilized allogeneic PBSCs IV on day 0.
• Graft-versus-host disease prophylaxis: Patients receive antithymocyte globulin IV over at least 10 hours on days -3 to -1. They also receive tacrolimus orally twice daily or IV continuously beginning on day -1 and continuing until up to day 55, followed by a taper until day 180 in the absence of graft-versus-host disease. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed annually.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Conditions

Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

anti-thymocyte globulin

Intervention Type: BIOLOGICAL

busulfan

Intervention Type: DRUG

fludarabine phosphate

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

tacrolimus

Intervention Type: DRUG

allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of 1 of the following myeloid malignancies:

• Chronic myelogenous leukemia meeting 1 of the following criteria:

• Chronic phase
• Accelerated phase
• Treated blast phase
• Acute myeloid leukemia meeting 1 of the following criteria:

• In remission
• In early relapse, defined as < 10% marrow blasts
• Myelodysplastic syndromes, including all risk groups
• Other myeloproliferative disorders
• HLA-A, -B, -C, -DRB1, and -DQB1 matched related or unrelated donor available

PATIENT CHARACTERISTICS:

• No other disease that would severely limit life expectancy
• AST ≤ 2 times normal
• Creatinine ≤ 2 times normal OR creatinine clearance ≥ 60 mL/min
• No cardiac insufficiency requiring treatment
• No symptomatic coronary artery disease
• PO_2 ≥ 70 mm Hg AND DLCO ≥ 70% of predicted OR PO _2 ≥ 80 mm Hg AND DLCO ≥ 60% of predicted
• HIV negative
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No post-transplantation growth factor during methotrexate administration

• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Principal Investigators

Paul V. O'Donnell, MD, PhD

Role: STUDY_CHAIR

Fred Hutchinson Cancer Center

Locations

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

FHCRC-2041.00

Identifier Type: -

Identifier Source: secondary_id

GEMZYME-FHCRC-2041.00

Identifier Type: -

Identifier Source: secondary_id

CDR0000488969

Identifier Type: REGISTRY

Identifier Source: secondary_id

2041.00

Identifier Type: -

Identifier Source: org_study_id