Intra-Osseous Co-Transplant of UCB and hMSC
Condition: Acute Lymphoblastic Leukemia; Acute Myelogenous Leukemia; Myelodysplastic Syndromes; Myelofibrosis; Relapsed Non-Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Relapsed Chronic Lymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Lymphoid Malignancies; Chronic Myelogenous Leukemia
MeSH terms: Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes
Study type: Interventional
Phase: Early Phase 1

Summary: 
      This clinical trial studies intra-osseous donor umbilical cord blood and mesenchymal stromal
      cell co-transplant in treating patients with hematologic malignancies. Giving low doses of
      chemotherapy and total-body irradiation before a co-transplant of donor umbilical cord blood
      and mesenchymal stromal cells into the bone (intra-osseous) helps stop the growth of cancer
      cells. It may also stop the patient's immune system from rejecting the donor's stem cells.
      The donated stem cells may replace the patient's immune cells and help destroy any remaining
      cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can
      also make an immune response against the body's normal cells. Giving cyclosporine and
      mycophenolate mofetil at the time of transplant may stop this from happening.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. To estimate the feasibility of combining intra-osseous umbilical cord blood (UCB)
      hematopoietic stem cells and human mesenchymal stromal cells (hMSC) following reduced
      intensity conditioning (RIC).

      SECONDARY OBJECTIVES:

      I. To estimate the time to engraftment of intra-osseous (IO) UCB transplant combined with
      hMSC following RIC.

      II. To estimate the safety profile of IO UBC transplant combined with hMSC.

      OUTLINE:

      REDUCED INTENSITY CONDITIONING: Patients receive cyclophosphamide intravenously (IV) over 2
      hours on day -6 and fludarabine phosphate IV on days -6 to -2 and undergo total body
      irradiation (TBI) on day -1.

      GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive cyclosporine orally (PO) or IV
      over 2 hours every 12 hours on beginning on days -5 to 100 with taper beginning on day 100
      and mycophenolate mofetil IV or PO twice daily (BID) on days -5 to 100.

      TRANSPLANT: Patients undergo intra-osseous UCB and hMSC co-transplant on day 0.

      After completion of study treatment, patients are followed up at days 28 and 100, and then at
      6, 9, and 12 months.
    

Intervention name(s): cyclophosphamide; fludarabine phosphate; total-body irradiation; cyclosporine; mycophenolate mofetil; umbilical cord blood transplantation; mesenchymal stem cell transplantation
Intervention type(s): Drug; Drug; Radiation; Drug; Drug; Procedure; Procedure
Intervention description(s): All patients will receive a single IV dose of 50 mg/kg of cyclophosphamide on day -6; Given by IV during prep at 40mg/m2 for 5 days; Undergo single fraction of reduced intensity conditioning (RIC) regimen of 200 cGy TBI without shielding on day -1; Initiated in patients on the day -5. Cyclosporine will be administered orally or intravenously at 2 mg/kg/dose every 12 hours for 2-hour period. Cyclosporine will continue until day +100; Given at 1g intravenously or orally twice daily from day -5 to +100, or as clinically indicated.; Following RIC, on day T+0, dimethylsulphoxide will be removed from the cord blood cells and given as transplant.; The total dosage of hMSC will be 2x10^6cells/kg (+/-20%).
Other intervention name(s): CPM; CTX; Cytoxan; Endoxan; Endoxana; 2-F-ara-AMP; Beneflur; Fludara; TBI; ciclosporin; cyclosporin; cyclosporin A; CYSP; Sandimmune; Cellcept; MMF; cord blood transplantation; transplantation, umbilical cord blood; UCB transplantation; hMSC transplantation
Intervention MeSH terms: Cyclosporine; Mycophenolic Acid; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Cyclosporins
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Total Body Irradiation; Human Mesenchymal Stromal Cells; hMSC; Cyclophosphamide; Fludarabine; Dimethyl Sulfoxide; DMSO; Cyclosporine; Mycophenolate Mofetil; MMF; Granulocyte- Colony Stimulating Factor; G-CSF; GVHD; Cancer; feasibility