A Pilot Study to Evaluate the Co-Infusion of Ex Vivo Expanded Cord Blood Cells With an Unmanipulated Cord Blood Unit in Patients Undergoing Cord Blood Transplant for Hematologic Malignancies
Condition: Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; 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); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Previously Treated Myelodysplastic Syndromes; Prolymphocytic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Splenic Marginal Zone Lymphoma; Stage I Adult Burkitt Lymphoma; Stage I Adult Diffuse Large Cell Lymphoma; Stage I Adult Diffuse Mixed Cell Lymphoma; Stage I Adult Immunoblastic Large Cell Lymphoma; Stage I Adult Lymphoblastic Lymphoma; Stage I Childhood Lymphoblastic Lymphoma; Stage I Grade 3 Follicular Lymphoma; Stage I Mantle Cell Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma
MeSH terms: Burkitt Lymphoma; Lymphoma; Leukemia; Leukemia, Myeloid; Multiple Myeloma; Leukemia, Myeloid, Acute; Lymphoma, Follicular; Preleukemia; Neoplasm Metastasis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, B-Cell, Marginal Zone; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Lymphoma, Large B-Cell, Diffuse; Hematologic Neoplasms; Lymphoma, Large-Cell, Immunoblastic; Plasmablastic Lymphoma; Lymphoma, Large-Cell, Anaplastic; Leukemia, Myeloid, Chronic-Phase; Lymphomatoid Granulomatosis; Leukemia, Myeloid, Accelerated Phase; Lymphoma, Extranodal NK-T-Cell; Leukemia, Prolymphocytic; Anemia; Myelodysplastic Syndromes; Anemia, Refractory; Anemia, Refractory, with Excess of Blasts; Syndrome; Recurrence
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase I multicenter feasibility trial is studying the safety and potential efficacy of
      infusing ex vivo expanded cord blood progenitors with one unmanipulated umbilical cord blood
      unit for transplantation following conditioning with fludarabine, cyclophosphamide and total
      body irradiation (TBI), and immunosuppression with cyclosporine and mycophenolate mofetil
      (MMF) for patients with hematologic malignancies. Chemotherapy, such as fludarabine and
      cyclophosphamide, and TBI 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 are more likely to
      recover more quickly if increased numbers of 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 unexpanded cord blood unit 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 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 co-infused with
      a second non-human leukocyte antigen (HLA)-identical cord blood graft following myeloablative
      therapy in patients with hematologic malignancies.

      II. Examine the in vivo persistence of the ex vivo expanded cord blood cells. The kinetics
      and durability of hematopoietic reconstitution (time to engraftment defined as the first of 2
      consecutive days in which the absolute neutrophil count [ANC] > 500) will be determined and
      the relative contribution to engraftment of the expanded cord blood cells and the
      unmanipulated cord blood cells in early and long-term engraftment will be determined by donor
      chimerisms.

      SECONDARY OBJECTIVES:

      I. Estimate the incidence and severity of acute and chronic graft-versus-host disease (GVHD)
      in patients receiving Notch-expanded 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 phenotype and function of immune cells recovering in
      patients receiving expanded and unmanipulated cord blood grafts.

      V. Obtain feasibility data on overnight shipment of ex vivo expanded progenitor cells for
      infusion in patients are distant sites.

      OUTLINE:

      MYELOABLATIVE CONDITIONING REGIMEN: Patients receive fludarabine intravenously (IV) over 1
      hour on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI twice
      daily (BID) on days -4 to -1.

      TRANSPLANTATION : On Day 0, patients undergo double-unit umbilical cord blood transplantation
      which includes the infusion of one unmanipulated (not expanded) cord blood unit followed 4
      hours later by infusion of one ex vivo-expanded cord blood unit.

      GRAFT-VERSUS-HOST-DISEASE PROPHYLAXIS: Patients initially receive cyclosporine IV beginning
      on day -3. Cyclosporine may be given orally when the patient can tolerate oral medications
      and has a normal gastrointestinal transit time. Cyclosporine is given until day 100, and may
      taper on day 101 if there is no graft versus host disease. Patients also receive MMF IV on
      days -3 to 5 and then may receive oral MMF beginning day 6 to 30. MMF is stopped at Day 30 or
      7 days after engraftment, whichever day is later, if no acute GVHD.

      After completion of study treatment, patients are followed up periodically for 2 years.
    

Intervention name(s): cyclophosphamide; fludarabine phosphate; cyclosporine; mycophenolate mofetil; ex-vivo umbilical cord blood expansion; double-unit umbilical cord blood transplantation; biopsy; immunologic technique; diagnostic laboratory biomarker analysis
Intervention type(s): Drug; Drug; Drug; Drug; Other; Procedure; Procedure; Other; Other
Intervention description(s): Given IV; Given IV; Given IV; Given IV or PO; Undergo double-unit umbilical cord blood transplantation; Undergo double-unit umbilical cord blood transplantation; Optional correlative studies; Correlative studies; Correlative studies
Other intervention name(s): CPM; CTX; Cytoxan; Endoxan; Endoxana; 2-F-ara-AMP; Beneflur; Fludara; ciclosporin; cyclosporin; cyclosporin A; CYSP; Sandimmune; Cellcept; MMF; biopsies; immunological laboratory methods; laboratory methods, immunological
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Cyclosporins
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment