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
Condition: Acute Biphenotypic Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia in Remission; Chronic Myelogenous Leukemia; Myelodysplastic Syndrome
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Biphenotypic, Acute; Myelodysplastic Syndromes; Syndrome
Study type: Interventional
Phase: Phase 2

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 description: 
      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.
    

Intervention name(s): Cyclophosphamide; Cyclosporine; Ex Vivo-Expanded Cord Blood Progenitor Cell Infusion; Fludarabine Phosphate; Mycophenolate Mofetil; Thiotepa; Total-Body Irradiation; Umbilical Cord Blood Transplantation
Intervention type(s): Drug; Drug; Biological; Drug; Drug; Drug; Radiation; Procedure
Intervention description(s): 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
Other intervention name(s): NLA101; Dilanubicel; Cord Blood Transplantation; UCB transplantation
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Thiotepa; Fludarabine; Fludarabine phosphate; Cyclosporins
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment