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

NCT01056614 | Completed Phase 2 DMC

• 4 other identifiers: 1913.00NCI-2009-01785P30CA015704P01HL036444
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Incidence of acute GvHD

  Maximum grade of acute GVHD and the number of therapies required to treat GVHD will be determined.

  Day 100 post-transplant

Secondary Outcomes (10)

• Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy

  At 3.25, 4.5, 6, 8, 11, and 24-hours after the beginning of infusion on days -5, -4, and -3

• Thymoglobulin pharmacokinetics

  On day -3 prior to the first dose, on day -1 one hour after completion of infusion and on day 1 at 0900

• Incidence of donor cell engraftment

  By day 100

• Incidence of system toxicities >= grade 3 as graded per CTCAE v.3

  Up to day 100 after transplantation

• Incidence of chronic GvHD

  Day 100

Study Arms (1)

Treatment (chemotherapy, PBSC transplant)

EXPERIMENTAL

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.

Drug: fludarabine phosphate; Drug: busulfan; Biological: anti-thymocyte globulin; Drug: tacrolimus; Drug: methotrexate; Procedure: peripheral blood stem cell transplantation; Procedure: allogeneic hematopoietic stem cell transplantation; Other: laboratory biomarker analysis

Interventions

fludarabine phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Treatment (chemotherapy, PBSC transplant)

busulfan DRUG

Given IV

Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon

Treatment (chemotherapy, PBSC transplant)

anti-thymocyte globulin BIOLOGICAL

Given IV

Also known as: ATG, ATGAM, lymphocyte immune globulin, Thymoglobulin

Treatment (chemotherapy, PBSC transplant)

tacrolimus DRUG

Given IV and orally

Also known as: FK 506, Prograf

Treatment (chemotherapy, PBSC transplant)

methotrexate DRUG

Given IV

Also known as: amethopterin, Folex, methylaminopterin, Mexate, MTX

Treatment (chemotherapy, PBSC transplant)

peripheral blood stem cell transplantation PROCEDURE

Undergo allogeneic PBSC transplant

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Treatment (chemotherapy, PBSC transplant)

allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo allogeneic PBSC transplant

Treatment (chemotherapy, PBSC transplant)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (chemotherapy, PBSC transplant)

Eligibility Criteria

• Age: Up to 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Accelerated Phase; Congenital Abnormalities; Blast Crisis; Leukemia, Myeloid, Chronic-Phase; Hematologic Neoplasms; Myeloproliferative Disorders; Leukemia, Myeloid, Acute

Interventions

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

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• H. Joachim Deeg

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2010
• First Posted: January 26, 2010
• Study Start: September 1, 2004
• Primary Completion: August 1, 2005
• Study Completion: April 1, 2016
• Last Updated: May 6, 2016

Record last verified: 2016-05

Locations

US (1)