Clinical Trial: Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Multi-center, Open-Label Randomized Study of Single or Double Myeloablative Cord Blood Transplantation With or Without Infusion of Off-The-Shelf Ex Vivo Expanded Cryopreserved Cord Blood Progenitor Ce

Brief Summary: 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.

Detailed Summary:

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
Sponsor: Fred Hutchinson Cancer Research Center

Current Primary Outcome: Time to engraftment defined as the first 2 consecutive days in which ANC >= 500 in both arms (standard myeloablative CBT with and without off-the-shelf expanded cord blood progenitors) [ Time Frame: Up to 2 years ]

The log-rank test will be used. Groups will be compared using Gray's test.


Original Primary Outcome: Time to engraftment (ANC greater than or equal to 500) in both arms (standard myeloablative CBT with and without off-the-shelf expanded cord blood progenitors) [ Time Frame: Up to 2 years ]

The log-rank test will be used.


Current Secondary Outcome:

  • Incidence and severity of acute and chronic GVHD [ Time Frame: Up to 2 years ]
  • Incidence of infectious complications [ Time Frame: Up to 100 days post-transplant ]
  • Non-relapse mortality [ Time Frame: Up to 100 days post-transplant ]
  • Overall survival [ Time Frame: Up to 2 years ]
  • Platelet engraftment (20k) [ Time Frame: Up to 2 years ]
    Groups will be compared using Gray's test.


Original Secondary Outcome:

  • Time to engraftment, defined as the first of 2 consecutive days in which ANC is at least 500 [ Time Frame: Up to 2 years ]
  • Relative contribution to engraftment of the expanded cord blood product and the unmanipulated cord blood unit(s) in early and long-term engraftment, determined by frequent determination of donor chimerism in the peripheral blood [ Time Frame: Up to 2 years ]
  • Time to ANC greater than or equal to 100 [ Time Frame: Up to 2 years ]
  • Time to ANC greater than or equal to 500 [ Time Frame: Up to 2 years ]
  • Time to platelet engraftment (20k) [ Time Frame: Up to 2 years ]
  • Time to platelet engraftment (50k) [ Time Frame: Up to 2 years ]
  • Duration of initial hospitalization [ Time Frame: Up to 2 years ]
  • Incidence of infectious complications [ Time Frame: Up to 100 days post-transplant ]
  • Non-relapse mortality (NRM) [ Time Frame: Day 200 ]
  • NRM [ Time Frame: 1 year ]
  • Incidence and severity of acute and chronic GVHD [ Time Frame: Up to 2 years ]
  • Infusional toxicity greater than or equal to grade 3 [ Time Frame: Up to 2 years ]
  • Graft failure (primary and secondary) [ Time Frame: Up to 2 years ]
  • Kinetics of immune system recovery as measured by T and B cell subsets, T cell receptor excision circles (TREC), spectratyping and T cell receptor (TCR) sequencing [ Time Frame: Up to 2 years ]


Information By: Fred Hutchinson Cancer Research Center

Dates:
Date Received: September 19, 2012
Date Started: December 11, 2012
Date Completion:
Last Updated: April 18, 2017
Last Verified: April 2017