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

NCT00346359 | Completed Phase 2

• 4 other identifiers: 2041.00FHCRC-2041.00GEMZYME-FHCRC-2041.00CDR0000488969
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Myeloproliferative Disorders; Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Keywords

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

Outcome Measures

Primary Outcomes (2)

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

• Incidence of donor engraftment

Secondary Outcomes (9)

• 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

Interventions

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

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

MeSH Terms

Conditions

Myeloproliferative Disorders; Graft vs Host Disease; Leukemia; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid, Chronic-Phase; Blast Crisis; Leukemia, Myeloid, Accelerated Phase; Leukemia, Myeloid, Acute; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Pdgfra-Associated Chronic Eosinophilic Leukemia; Primary Myelofibrosis; Leukemia, Neutrophilic, Chronic; Congenital Abnormalities

Interventions

Antilymphocyte Serum; Busulfan; fludarabine phosphate; Methotrexate; Tacrolimus; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cell Transformation, Neoplastic; Carcinogenesis; Neoplastic Processes; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Macrolides; Lactones; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Study Officials

• Paul V. O'Donnell, MD, PhD

  Fred Hutchinson Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 28, 2006
• First Posted: June 29, 2006
• Study Start: March 1, 2006
• Study Completion: November 1, 2007
• Last Updated: May 14, 2010

Record last verified: 2010-05

Locations

US (1)