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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00346359
• Other study ID #: 2041.00
• Secondary ID: FHCRC-2041.00GEM
• Status: Completed
• Phase: Phase 2
• First received: June 28, 2006
• Last updated: May 12, 2010
• Start date: March 2006
• Est. completion date: November 2007

Study information

• Verified date: May 2010
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 65 Years

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myeloproliferative Disorders
• Graft Versus Host Disease
• Graft vs Host Disease
• Leukemia
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Diseases
• Myeloproliferative Disorders
• Preleukemia

Intervention

Biological:
• anti-thymocyte globulin

Drug:
• busulfan

• fludarabine phosphate

• methotrexate

• tacrolimus

Procedure:
• allogeneic hematopoietic stem cell transplantation

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of acute graft-versus-host disease (GVHD)			No
Primary	Incidence of donor engraftment			No
Secondary	Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy			No
Secondary	Pharmacokinetics of antithymocyte globulin			No
Secondary	Pharmacokinetics of fludarabine phosphate and its effect on lymphocytes			No
Secondary	Incidence of specific toxic effects = grade 3			Yes
Secondary	Incidence and severity of chronic GVHD			No
Secondary	Incidence of nonrelapsing mortality at 100 days and at 1 year after transplantation			No
Secondary	Incidence of relapse			No
Secondary	Relapse-free survival			No
Secondary	Incidence of Epstein-Barr virus activation and post-transplantation lymphoproliferative disease			No