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

Sponsor

Fred Hutchinson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00346359

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloproliferative Disorders Graft Versus Host Disease Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Biological: anti-thymocyte globulin Drug: busulfan Drug: fludarabine phosphate Drug: methotrexate Drug: tacrolimus Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Conditioning For Hematopoietic Cell Transplantation With Fludarabine Plus Targeted IV Busulfan and GVHD Prophylaxis With Thymoglobulin, Tacrolimus and Methotrexate in Patients With Myeloid Malignancies

Study Start Date :

Mar 1, 2006

Actual Study Completion Date :

Nov 1, 2007

Outcome Measures

Primary Outcome Measures

Incidence and severity of acute graft-versus-host disease (GVHD) []
Incidence of donor engraftment []

Secondary Outcome Measures

Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy []
Pharmacokinetics of antithymocyte globulin []
Pharmacokinetics of fludarabine phosphate and its effect on lymphocytes []
Incidence of specific toxic effects ≥ grade 3 []
Incidence and severity of chronic GVHD []
Incidence of nonrelapsing mortality at 100 days and at 1 year after transplantation []
Incidence of relapse []
Relapse-free survival []
Incidence of Epstein-Barr virus activation and post-transplantation lymphoproliferative disease []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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