Overview

This trial is active, not recruiting.

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
Treatments fludarabine phosphate, busulfan, anti-thymocyte globulin, tacrolimus, methotrexate, peripheral blood stem cell transplantation, allogeneic hematopoietic stem cell transplantation, laboratory biomarker analysis
Phase phase 2
Sponsor Fred Hutchinson Cancer Research Center
Collaborator National Heart, Lung, and Blood Institute (NHLBI)
Start date September 2004
End date August 2005
Trial size 23 participants
Trial identifier NCT01056614, 1913.00, NCI-2009-01785, P01HL036444, P30CA015704

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(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.
fludarabine phosphate 2-F-ara-AMP
Given IV
busulfan BSF
Given IV
anti-thymocyte globulin ATG
Given IV
tacrolimus FK 506
Given IV and orally
methotrexate amethopterin
Given IV
peripheral blood stem cell transplantation PBPC transplantation
Undergo allogeneic PBSC transplant
allogeneic hematopoietic stem cell transplantation
Undergo allogeneic PBSC transplant
laboratory biomarker analysis
Correlative studies

Primary Outcomes

Measure
Incidence of acute GvHD
time frame: Day 100 post-transplant

Secondary Outcomes

Measure
Pharmacokinetics of IV busulfan including interdose variability and evaluation of a limited sampling strategy
time frame: At 3.25, 4.5, 6, 8, 11, and 24-hours after the beginning of infusion on days -5, -4, and -3
Thymoglobulin pharmacokinetics
time frame: 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
time frame: By day 100
Incidence of system toxicities >= grade 3 as graded per CTCAE v.3
time frame: Up to day 100 after transplantation
Incidence of chronic GvHD
time frame: Day 100
Incidence of non-relapse mortality defined as death without history of post-transplant relapse
time frame: At day 100
Incidence of non-relapse mortality defined as death without history of post-transplant relapse
time frame: At 1 year
Incidence of relapse
time frame: At 1 year
Relapse-free survival
time frame: At 1 year
Incidence of EBV activation defined as an increase in plasma EBV DNA to >= 1000 copies/mL as determined by quantitative polymerase chain reaction (PCR)
time frame: Up to 1 year

Eligibility Criteria

Male or female participants up to 60 years old.

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

Additional Information

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
Principal investigator H. Joachim Deeg
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.
Trial information was received from ClinicalTrials.gov and was last updated in November 2015.
Information provided to ClinicalTrials.gov by Fred Hutchinson Cancer Research Center.