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

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00346359

Purpose

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	Intervention	Phase
Chronic Myeloproliferative Disorders Graft Versus Host Disease Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Drug: 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 II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood

Drug Information available for: Methotrexate Fludarabine Fludarabine monophosphate Tacrolimus Tacrolimus anhydrous Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Incidence and severity of acute graft-versus-host disease (GVHD) [ Designated as safety issue: No ]
Incidence of donor engraftment [ Designated as safety issue: No ]

Secondary Outcome Measures:

Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy [ Designated as safety issue: No ]
Pharmacokinetics of antithymocyte globulin [ Designated as safety issue: No ]
Pharmacokinetics of fludarabine phosphate and its effect on lymphocytes [ Designated as safety issue: No ]
Incidence of specific toxic effects ≥ grade 3 [ Designated as safety issue: Yes ]
Incidence and severity of chronic GVHD [ Designated as safety issue: No ]
Incidence of nonrelapsing mortality at 100 days and at 1 year after transplantation [ Designated as safety issue: No ]
Incidence of relapse [ Designated as safety issue: No ]
Relapse-free survival [ Designated as safety issue: No ]
Incidence of Epstein-Barr virus activation and post-transplantation lymphoproliferative disease [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	March 2006
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

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

Ages Eligible for Study:	up to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00346359

Locations

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

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Paul V. O'Donnell, MD, PhD

Fred Hutchinson Cancer Research Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000488969, FHCRC-2041.00, GEMZYME-FHCRC-2041.00
Study First Received:	June 28, 2006
Last Updated:	May 23, 2008
ClinicalTrials.gov Identifier:	NCT00346359
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Juvenile myelomonocytic leukemia
Blast Crisis
Precancerous Conditions
Chronic myelogenous leukemia
Chronic myelomonocytic leukemia
Graft versus host disease
Tacrolimus
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid, Acute
Leukemia
Preleukemia
Chronic Myeloproliferative Disorders
Neoplasm Metastasis
Methotrexate
Acute myeloid leukemia, adult

Congenital Abnormalities
Acute myelocytic leukemia
Myelodysplastic syndromes
Myelofibrosis
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Myelodysplasia
Myelodysplastic Syndromes
Acute myelogenous leukemia
Myeloproliferative Disorders
Fludarabine monophosphate
Leukemia, Myelomonocytic, Juvenile
Leukemia, Myeloid
Recurrence

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Pathologic Processes
Syndrome
Therapeutic Uses
Abortifacient Agents
Alkylating Agents
Dermatologic Agents

Nucleic Acid Synthesis Inhibitors
Disease
Neoplasms by Histologic Type
Immune System Diseases
Enzyme Inhibitors
Abortifacient Agents, Nonsteroidal
Folic Acid Antagonists
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents

ClinicalTrials.gov processed this record on January 14, 2009