Infusion of Off-the-Shelf Ex Vivo Expanded Cryopreserved Cord Blood Progenitor Cells to Augment Single or Double Myeloablative Cord Blood Transplantation in Patients With Hematologic Malignancies
I. Examine the safety and toxicity when ex vivo expanded cord blood cells are infused as an
off-the-shelf non-HLA matched product with the goal of providing rapid but transient
myelopoiesis in the setting of a single or double umbilical cord blood transplant.
II. Examine the in vivo persistence of the ex vivo expanded cord blood product. The kinetics
and durability of hematopoietic reconstitution will be determined and the relative
contribution to engraftment of the expanded cord blood product and the unmanipulated cord
blood unit(s) in early and long-term engraftment will be determined by frequent
determination of donor chimerisms in the peripheral blood.
SECONDARY OBJECTIVES I. Estimate the incidence and severity of acute and chronic
graft-versus-host-disease (GVHD) in patients receiving off-the-shelf ex vivo expanded and
cryopreserved 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 incidence of infections/viral reactivation from the start
of conditioning to 100 days post transplant and then at 6 months, 1 year and 2 years post
transplant as possible.
V. Obtain preliminary data on the phenotype and function of immune cells recovering in
patients receiving expanded and unmanipulated cord blood grafts.
VI. Examination of possible immunologic factors leading to emergence of a dominant unit.
MYELOABLATIVE CONDITIONING: Patients receive fludarabine intravenously (IV) over 1 hour on
days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo total-body
irradiation (TBI) twice daily on days -4 to -1.
TRANSPLANTATION: Patients undergo unmanipulated single- or double-unit umbilical cord blood
transplantation on day 0 and receive ex vivo-expanded cord blood progenitor cells IV over 4
hours following the last unmanipulated cord blood infusion.
GVHD PROPHYLAXIS: Patients initially receive cyclosporine (CSP) IV over 1 hour beginning on
day -3. CSP may be given orally (PO) when the patient can tolerate oral medications and has
a normal gastrointestinal transit time. CSP is given until day 100, and may taper on day 101
if there is no graft versus host disease. Patients also receive mycophenolate mofetil (MMF)
IV every 8 hours on days 0 to 7 and then may receive MMF PO beginning day 8 to 30. MMF is
continued for a minimum of 30 days or until 7 days after blood counts recover whichever is
later. If there is no evidence of acute GVHD and donor CD3 engraftment is at least 50% from
one donor MMF may be tapered.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Time to neutrophil and platelet engraftment
Defined as the first of 2 consecutive days in which the absolute neutrophil count (ANC) >= 500.
By day 30
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
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