Clinical Trial: Infusion of Off-the-Shelf Expanded Cord Blood Cells to Augment Cord Blood Transplant in Patients With Hematologic Malignancies

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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

Brief Summary: This phase II trial is studying the safety and potential efficacy of infusing non-human leukocyte antigen matched ex vivo expanded cord blood progenitors with one or two unmanipulated umbilical cord blood units for transplantation following conditioning with fludarabine phosphate, cyclophosphamide and total body irradiation, and immunosuppression with cyclosporine and mycophenolate mofetil for patients with hematologic malignancies. Chemotherapy, such as fludarabine phosphate and cyclophosphamide, and total-body irradiation given before an umbilical cord blood transplant stops the growth of leukemia cells and works to prevent the patient's immune system from rejecting the donor's stem cells. The healthy stem cells from the donor's umbilical cord blood help the patient's bone marrow make new red blood cells, white blood cells, and platelets. It may take several weeks for these new blood cells to grow. During that period of time, patients are at increased risk for bleeding and infection. Faster recovery of white blood cells may decrease the number and severity of infections. Studies have shown that counts recover more quickly when more cord blood cells are given with the transplant. We have developed a way of growing or "expanding" the number of cord blood cells in the lab so that there are more cells available for transplant. We are doing this study to find out whether or not giving these expanded cells along with one or two unexpanded cord blood units is safe and if use of expanded cells can decrease the time it takes for white blood cells to recover after transplant. We will study the time it takes for blood counts to recover, which of the two or three cord blood units makes up the patient's new blood system, and how quickly immune system cells return.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Examine the safety and toxicity when ex vivo expanded cord blood cells are infused as an off-the-shelf non-human leukocyte antigen (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 possi
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome:

  • Time to neutrophil engraftment [ Time Frame: By day 30 ]
    Defined as the first of 2 consecutive days in which the absolute neutrophil count (ANC) >= 500.
  • Time to platelet engraftment [ Time Frame: By day 30 ]
  • Overall survival [ Time Frame: Day 100 ]
  • Overall survival [ Time Frame: Day 180 ]
  • Overall survival [ Time Frame: 1 year ]
  • Overall survival [ Time Frame: 2 years ]
  • Event-free survival [ Time Frame: Day 100 ]
  • Event-free survival [ Time Frame: Day 180 ]
  • Event-free survival [ Time Frame: 1 year ]
  • Event-free survival [ Time Frame: 2 years ]
  • Incidence of severe (grades 3-4) acute GVHD [ Time Frame: Up to 4 years ]
  • Incidence of grade greater than or equal to 3 infusional toxicity [ Time Frame: By day 100 ]
    Toxicities will be graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0.
  • Primary graft failure [ Time Frame: By day 42 ]
    Defined as failure to achieve ANC >= 500/mm^3 of donor origin.
  • Secondary graft failure [ Time Frame: Up to 4 years ]


Original Primary Outcome:

  • Time to neutrophil and platelet engraftment [ Time Frame: At day 100 ]
  • Overall survival and EFS [ Time Frame: At day 100 ]
  • Severe (Grade 3-4) acute graft versus host disease [ Time Frame: At day 100 ]
  • Severe (Grade 3-4) acute graft versus host disease [ Time Frame: At day 180 ]
  • Severe (Grade 3-4) acute graft versus host disease [ Time Frame: At 1 year ]
  • Overall survival and EFS [ Time Frame: At day 180 ]
  • Overall survival and EFS [ Time Frame: At 1 year ]
  • Overall survival and EFS [ Time Frame: At 2 years ]
  • Severe (Grade 3-4) acute graft versus host disease [ Time Frame: At 2 years ]
  • Grade >= infusional toxicity [ Time Frame: At day 100 ]
  • Graft Failure Primary and Secondary [ Time Frame: At day 100 ]


Current Secondary Outcome:

Original Secondary Outcome:

Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: August 3, 2010
Date Started: August 2010
Date Completion:
Last Updated: April 5, 2017
Last Verified: April 2017