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

Information source: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Intervention: anti-thymocyte globulin (Biological); busulfan (Drug); fludarabine phosphate (Drug); methotrexate (Drug); tacrolimus (Drug); allogeneic hematopoietic stem cell transplantation (Procedure); peripheral blood stem cell transplantation (Procedure)

Phase: Phase 2

Status: Completed

Sponsored by: Fred Hutchinson Cancer Research Center

Official(s) and/or principal investigator(s):
Paul V. O'Donnell, MD, PhD, Study Chair, Affiliation: Fred Hutchinson Cancer Research Center

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.

Clinical Details

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 design: Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Incidence and severity of acute graft-versus-host disease (GVHD)

Incidence of donor engraftment

Secondary outcome:

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

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.

Eligibility

Minimum age: N/A. Maximum age: 65 Years. Gender(s): Both.

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

Locations and Contacts

Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, United States
Additional Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: March 2006
Last updated: May 12, 2010

Page last updated: August 20, 2015

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