A Pilot Study to Evaluate the Co-infusion of Ex Vivo Expanded Umbilical Cord Blood Progenitors With an Unmanipulated Cord Blood Graft in Patients Undergoing Umbilical Cord Blood Transplantation for Hematologic Malignancies
I. Examine the safety and toxicity when ex vivo expanded cord blood cells are co-infused
with a second non-human leukocyte antigen (HLA)-identical cord blood graft following
myeloablative therapy in patients with hematologic malignancies.
II. Examine the in vivo persistence of the ex vivo expanded cord blood cells. The kinetics
and durability of hematopoietic reconstitution (time to engraftment defined as the first of
2 consecutive days in which the absolute neutrophil count [ANC] > 500) will be determined
and the relative contribution to engraftment of the expanded cord blood cells and the
unmanipulated cord blood cells in early and long-term engraftment will be determined by
I. Estimate the incidence and severity of acute and chronic graft-versus-host disease (GVHD)
in patients receiving Notch-expanded cord blood cells.
II. Estimate the incidence of transplant related mortality at day 100.
III. Estimate the incidence of malignant relapse and probabilities of overall and event-free
survival at 1 and 2 years post transplant.
IV. Obtain preliminary data on the phenotype and function of immune cells recovering in
patients receiving expanded and unmanipulated cord blood grafts.
V. Obtain feasibility data on overnight shipment of ex vivo expanded progenitor cells for
infusion in patients are distant sites.
MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine intravenously (IV) over 1
hour on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI twice
daily (BID) on days -4 to -1.
TRANSPLANTATION : On Day 0, patients undergo double-unit umbilical cord blood
transplantation which includes the infusion of one unmanipulated (not expanded) cord blood
unit followed 4 hours later by infusion of one ex vivo-expanded cord blood unit.
GRAFT-VERSUS-HOST-DISEASE PROPHYLAXIS: Patients initially receive cyclosporine IV beginning
on day -3. Cyclosporine may be given orally when the patient can tolerate oral medications
and has a normal gastrointestinal transit time. Cyclosporine is given until day 100, and may
taper on day 101 if there is no graft versus host disease. Patients also receive MMF IV on
days -3 to 5 and then may receive oral MMF beginning day 6 to 30. MMF is stopped at Day 30
or 7 days after engraftment, whichever day is later, if no acute GVHD.
After completion of study treatment, patients are followed up periodically for 2 years.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Severe (grades 3 and 4) acute GVHD
Up to day 100
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|
|University of Colorado||Denver, Colorado 80217|
|City of Hope Medical Center||Duarte, California 91010|
|University of Colorado Cancer Center - Anschutz Cancer Pavilion||Aurora, Colorado 80045|