This randomized phase II trial studies how well donor umbilical cord blood transplant with or without ex-vivo expanded cord blood progenitor cells works in treating patients with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, or myelodysplastic syndromes. Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's cells. When the healthy stem cells and ex-vivo expanded cord blood progenitor cells are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. It is not yet known whether giving donor umbilical cord blood transplant plus ex-vivo expanded cord blood progenitor cells is more effective than giving a donor umbilical cord blood transplant alone.
PRIMARY OBJECTIVES: I. Compare the time to neutrophil engraftment (absolute neutrophil count \[ANC\] \>= 500) in patients receiving a standard of care myeloablative cord blood transplant (CBT) augmented with an off-the-shelf pre-expanded and cryopreserved cord blood product to those who do not receive the product. SECONDARY OBJECTIVES: I. Provide initial data on clinical and economic benefit, such as time to platelet engraftment, duration of initial hospitalization, transplant-related mortality (TRM), death without engraftment, and incidence of severe infections in the first 100 days post-transplant. II. The kinetics of immune system recovery will also be evaluated in both arms. OUTLINE: Patients are randomized to 1 of 2 treatment arms. Standard of Care Arm: CONDITIONING REGIMEN: One of two possible conditioning regimens is chosen by the attending physician: Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -8 to -6, cyclophosphamide IV on days -7 to -6., and undergo high dose total-body irradiation (TBI) twice daily (BID) on days -4 to -1 OR, patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -2, cyclophosphamide IV on day -6, thiotepa IV over 4 hours on days -5 to -4, and undergo middle intensity TBI once daily (QD) on days -2 to -1. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated umbilical cord blood (UCB) transplant on day 0. GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine IV over 1 hour BID (adults) or thrice daily (TID) (children) or orally (PO) on days -3 to 100 with taper beginning on day 101. Patients also receive mycophenolate mofetil (MMF) IV TID on days 0-7 then may receive MMF PO TID. Patients remain on MMF TID for a minimum of 30 days, and then may begin taper if there is no evidence of GVHD and are well-engrafted from one donor unit. Experimental Arm: CONDITIONING REGIMEN: Patients receive the conditioning regimen chosen by the attending physician as in Standard of Care Arm. TRANSPLANT: Patients undergo single-unit or double-unit unmanipulated UCB transplant on day 0. Patients also receive an infusion of ex vivo-expanded cord blood progenitors at least 4 hours after completion of UCB transplant. GVHD PROPHYLAXIS: Patients receive cyclosporine IV or PO and mycophenolate mofetil IV or PO as in Standard of Care Arm. After completion of study treatment, patients are followed up periodically for 2 years.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
163
Given IV
Given IV or PO
Given IV
Given IV
Given IV or PO
Given IV
Undergo high dose or middle intensity TBI
Undergo single-unit or double-unit unmanipulated umbilical cord blood transplant
City of Hope Comprehensive Cancer Center
Duarte, California, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States
University of Colorado
Denver, Colorado, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Mount Sinai Hospital
New York, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States
Time to Neutrophil Engraftment
First of two consecutive days with absolute neutrophil count (ANC) equal to or greater than 500 cell/microliter measured from day of transplant.
Time frame: Up to 55 days post-transplant
Time to Platelet Engraftment (20k)
First day of seven consecutive days with platelet count equal to or greater than 20,000 cells/microliter without platelet transfusions measured from day of transplant.
Time frame: Up to 100 days post-transplant
Overall Survival
Time frame: Up to 2 years
Non-relapse Mortality
Time frame: Up to 2 years
Proportion of Patients With Severe Acute Graft Versus Host Disease
Time frame: Up to 100 days post-transplant
Proportion of Participants With Chronic Graft Versus Host Disease
Time frame: Up to 2 years
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