Infusion of Off-the-Shelf Expanded Cord Blood Cells to Augment Cord Blood Transplant in Patients With Hematologic Malignancies
Condition: Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Hematologic Neoplasms; Leukemia, Myeloid, Chronic-Phase; Leukemia, Myeloid, Accelerated Phase; Anemia; Myelodysplastic Syndromes; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Syndrome
Study type: Interventional
Phase: Phase 2

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 description: 
      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 possible immunologic factors leading to emergence of a dominant unit.

      OUTLINE:

      MYELOABLATIVE CONDITIONING: Patients receive fludarabine phosphate 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 cluster of differentiation (CD)3
      engraftment is at least 50% from one donor MMF may be tapered.
    

Intervention name(s): umbilical cord blood transplantation; fludarabine phosphate; cyclophosphamide; ex vivo-expanded cord blood progenitor cell infusion; total-body irradiation; cyclosporine; mycophenolate mofetil; laboratory biomarker analysis
Intervention type(s): Procedure; Drug; Drug; Biological; Radiation; Drug; Drug; Other
Intervention description(s): Undergo unmanipulated umbilical cord blood transplant; Given IV; Given IV; Undergo ex-vivo expanded cryopreserved cord blood progenitor cells; Undergo TBI; Given IV; Given IV and PO; Correlative studies
Other intervention name(s): cord blood transplantation; transplantation, umbilical cord blood; UCB transplantation; 2-F-ara-AMP; Beneflur; Fludara; CPM; CTX; Cytoxan; Endoxan; Endoxana; Dilanubicel; NLA101; TBI; ciclosporin; cyclosporin; cyclosporin A; CYSP; Sandimmune; Cellcept; MMF
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Cyclosporins
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment