Fludarabine Phosphate, Busulfan, and Anti-Thymocyte Globulin Followed By Donor Peripheral Blood Stem Cell Transplant, Tacrolimus, and Methotrexate in Treating Patients With Myeloid Malignancies

NCT ID: NCT01056614

Last Updated: 2016-05-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-09-30
• Study Completion Date: 2016-04-30

Brief Summary

This phase II trial is studying the side effects and how well giving fludarabine phosphate, busulfan, anti-thymocyte globulin followed by donor peripheral blood stem cell transplant, tacrolimus, and methotrexate works in treating patients with myeloid malignancies. Giving chemotherapy, such as fludarabine phosphate and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving anti-thymocyte globulin before transplant and tacrolimus and methotrexate after transplant may stop this from happening.

Detailed Description

PRIMARY OBJECTIVE:

I. Determine the incidence and severity of acute graft-versus-host disease (GvHD).

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetics of intravenous (IV) busulfan including interdose variability and evaluation of a limited sampling strategy.

II. Determine thymoglobulin (anti-thymocyte globulin) pharmacokinetics.

III. Determine the incidence of donor engraftment.

IV. Determine system toxicities >= grade 3 per Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 3.

V. Determine the incidence and severity of chronic GvHD.

VI. Determine the incidence of non-relapse mortality at day +100 and at 1 year (yr).

VII. Determine the incidence of relapse.

VIII. Determine relapse-free survival.

IX. Determine the incidence of Epstein-Barr virus (EBV) activation.

OUTLINE:

Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -9 to -6, busulfan IV over 3 hours on days -5 to -2, and anti-thymocyte globulin IV over 6 hours on days -3 and -2 and over 4 hours on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplant on day 0. Patients then receive tacrolimus IV continuously or orally (PO) every 12 hours beginning on day -1 and taper to day 180 and methotrexate IV on days 1, 3, 6, and 11.

After completion of study treatment, patients are followed at 1 year.

Conditions

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); 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); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Hematopoietic/Lymphoid Cancer; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (chemotherapy, PBSC transplant)

Patients receive fludarabine phosphate IV over 30 minutes on days -9 to -6, busulfan IV over 3 hours on days -5 to -2, and anti-thymocyte globulin IV over 6 hours on days -3 and -2 and over 4 hours on day -1. Patients undergo allogeneic PBSC transplant on day 0. Patients then receive tacrolimus IV continuously or PO every 12 hours beginning on day -1 and taper to day 180 and methotrexate IV on days 1, 3, 6, and 11.

Group Type: EXPERIMENTAL

fludarabine phosphate

Intervention Type: DRUG

Given IV

busulfan

Intervention Type: DRUG

Given IV

anti-thymocyte globulin

Intervention Type: BIOLOGICAL

Given IV

tacrolimus

Intervention Type: DRUG

Given IV and orally

methotrexate

Intervention Type: DRUG

Given IV

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Undergo allogeneic PBSC transplant

allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Undergo allogeneic PBSC transplant

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

fludarabine phosphate

Given IV

Intervention Type: DRUG

busulfan

Given IV

Intervention Type: DRUG

anti-thymocyte globulin

Given IV

Intervention Type: BIOLOGICAL

tacrolimus

Given IV and orally

Intervention Type: DRUG

methotrexate

Given IV

Intervention Type: DRUG

peripheral blood stem cell transplantation

Undergo allogeneic PBSC transplant

Intervention Type: PROCEDURE

allogeneic hematopoietic stem cell transplantation

Undergo allogeneic PBSC transplant

Intervention Type: PROCEDURE

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

2-F-ara-AMP; Beneflur; Fludara; BSF; BU; Misulfan; Mitosan; Myeloleukon; ATG; ATGAM; lymphocyte immune globulin; Thymoglobulin; FK 506; Prograf; amethopterin; Folex; methylaminopterin; Mexate; MTX; PBPC transplantation; PBSC transplantation; peripheral blood progenitor cell transplantation; transplantation, peripheral blood stem cell

Eligibility Criteria

Inclusion Criteria

• Chronic myelogenous leukemia in chronic phase, accelerated phase and treated blast phase (CP2)
• Acute myeloid leukemia (AML) in remission or early relapse (< 10% marrow blasts)
• Myelodysplastic syndromes (MDS) ( all risk groups)
• Other myeloproliferative disorders
• DONOR: related or unrelated donors matched for human leukocyte antigen (HLA)-A, B, C, DRB1, and DQB1 defined by high resolution deoxyribonucleic acid (DNA) typing or mismatched for a single HLA-A, B, C, DRB1 or DQB1 allele
• DONOR: donor must consent to peripheral blood stem cell (PBSC) mobilization with granulocyte colony-stimulating factor (G-CSF) and leukapheresis; related donors will be collected at Fred Hutchinson Cancer Research Center (FHCRC), while unrelated donors will be collected through the National Marrow Donor Program (NMDP) or other donor centers
• DONOR: Age 12-75 yrs

Exclusion Criteria

• Cardiac insufficiency requiring treatment or symptomatic coronary artery disease
• Hepatic disease, with aspartate aminotransferase (AST) > 2 times normal
• Severe hypoxemia, oxygen partial pressure (pO2) < 70 mm Hg, with decreased diffusion capacity of carbon monoxide (DLCO) < 70% of predicted; or mild hypoxemia, pO2 < 80 mm Hg with severely decreased DLCO < 60% of predicted
• Impaired renal function (creatinine > 2 times normal or estimated creatinine clearance < 60 ml/min)

• MALE: ([140 -age in years] x ideal body weight [kg])/72 x serum creatinine (SCr) (mg/dL)
• FEMALE: .85 x ([140-age in years] x ideal body weight [kg])/72 x SCr (mg/dL)
• Human immunodeficiency virus (HIV)-positive patients due to risk of reactivation or acceleration of HIV replication
• Female patients who are pregnant or breast feeding
• Life expectancy severely limited by diseases other than malignancy
• DONOR: donors who for any reason are unable to tolerate the mobilization and leukapheresis procedure
• DONOR: donors who are HIV-positive, or hepatitis B or C antigen-positive
• DONOR: female donors who have a positive pregnancy test

• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

H. Joachim Deeg

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

Other Identifiers

NCI-2009-01785

Identifier Type: REGISTRY

Identifier Source: secondary_id

1913.00

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P01HL036444

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1913.00

Identifier Type: -

Identifier Source: org_study_id