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


Phase 2
N/A
65 Years
Not Enrolling
Both
Chronic Myeloproliferative Disorders, Graft Versus Host Disease, Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

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Trial Information

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


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.

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

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Safety Issue:

No

Principal Investigator

Paul V. O'Donnell, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Fred Hutchinson Cancer Research Center

Authority:

United States: Federal Government

Study ID:

2041.00

NCT ID:

NCT00346359

Start Date:

March 2006

Completion Date:

November 2007

Related Keywords:

  • Chronic Myeloproliferative Disorders
  • Graft Versus Host Disease
  • Leukemia
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • graft versus host disease
  • chronic phase chronic myelogenous leukemia
  • childhood chronic myelogenous leukemia
  • blastic phase chronic myelogenous leukemia
  • accelerated phase chronic myelogenous leukemia
  • relapsing chronic myelogenous leukemia
  • adult acute myeloid leukemia in remission
  • recurrent adult acute myeloid leukemia
  • childhood acute myeloid leukemia in remission
  • recurrent childhood acute myeloid leukemia
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • atypical chronic myeloid leukemia
  • chronic myelomonocytic leukemia
  • juvenile myelomonocytic leukemia
  • myelodysplastic/myeloproliferative disease, unclassifiable
  • secondary acute myeloid leukemia
  • chronic eosinophilic leukemia
  • chronic idiopathic myelofibrosis
  • chronic neutrophilic leukemia
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(15;17)(q22;q12)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • childhood myelodysplastic syndromes
  • Graft vs Host Disease
  • Leukemia
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109