Clinical Trials /

Intra-Osseous Co-Transplant of UCB and hMSC

NCT02181478

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Chronic Lymphocytic Leukemia
  • Chronic Myeloid Leukemia
  • Hodgkin Lymphoma
  • Myelodysplastic Syndromes
  • Myelofibrosis
  • Non-Hodgkin Lymphoma
Recruiting Status:

Recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Intra-Osseous Co-Transplant of UCB and hMSC
  • Official Title: Intra-osseous Co-transplant of Cord Blood and Mesenchymal Stromal Cells: A Feasibility Study

Clinical Trial IDs

  • ORG STUDY ID: CASE1Z14
  • SECONDARY ID: NCI-2014-01316
  • SECONDARY ID: CASE1Z14
  • SECONDARY ID: P30CA043703
  • NCT ID: NCT02181478

Conditions

  • 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

Interventions

DrugSynonymsArms
cyclophosphamideCPM, CTX, Cytoxan, Endoxan, EndoxanaTreatment (intra-osseous UCB with hMSC co-transplant)
fludarabine phosphate2-F-ara-AMP, Beneflur, FludaraTreatment (intra-osseous UCB with hMSC co-transplant)
cyclosporineciclosporin, cyclosporin, cyclosporin A, CYSP, SandimmuneTreatment (intra-osseous UCB with hMSC co-transplant)
mycophenolate mofetilCellcept, MMFTreatment (intra-osseous UCB with hMSC co-transplant)

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (intra-osseous UCB with hMSC co-transplant)ExperimentalREDUCED INTENSITY CONDITIONING: Patients receive cyclophosphamide IV over 2 hours on day -6 and fludarabine phosphate IV on days -6 to -2 and undergo total-body irradiation on day -1. GVHD PROPHYLAXIS: Patients receive cyclosporine 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 BID on days -5 to 100. TRANSPLANT: Patients undergo a co-transplantation of an intra-osseous umbilical cord blood transplantation and a mesenchymal stem cell transplantation on day 0.
  • cyclophosphamide
  • fludarabine phosphate
  • cyclosporine
  • mycophenolate mofetil

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must have one of the following malignancies:

               -  Acute myelogenous leukemia (AML): high-risk AML including:

                    -  Antecedent hematological disease (e.g., myelodysplasia [MDS])

                    -  Treatment-related leukemia

                    -  Complete remission (first complete remission [CR1]) with poor-risk
                       cytogenetics or molecular markers (e.g. fms-related tyrosine kinase 3 [Flt
                       3] mutation, 11q23, del 5, del 7, complex cytogenetics)

                    -  Second complete remission (CR2) or third complete remission (CR3)

                    -  Induction failure or first relapse with either

                         -  ≤ 10% blasts in the marrow and/or

                         -  ≤ 5% blasts in the peripheral blood

               -  Acute lymphoblastic leukemia (ALL)

                    -  High-risk CR1 including:

                    -  Poor-risk cytogenetics (e.g., Philadelphia chromosome t(9;22)or 11q23
                       rearrangements)

                    -  Presence of minimal disease by flow cytometry after 2 or more cycles of
                       chemotherapy

                    -  No complete remission (CR) within 4 weeks of initial treatment

                    -  Induction failure

                    -  CR2 or CR3 with either:

                         -  ≤ 10% blasts in the marrow and/or

                         -  ≤ 5% blasts in the peripheral blood

               -  Myelodysplastic syndromes (MDS), Intermediate-1 (INT-1), intermediate-2 (INT-2)
                  or high Revised International Prognostic Scoring System (IPSS-R) score that has
                  failed at least 1 first line therapy

               -  Myelofibrosis (MF):

                    -  Intermediate-2 or high risk by Dynamic International Prognostic Scoring
                       System (DIPSS)-plus

                    -  Monosomal karyotype

                    -  Presence of inv(3)/i(17q) abnormalities

                    -  Other unfavorable karyotype OR leukocytes ≥40 X 10^9/L AND

                    -  Circulating blasts ≤ 9%

               -  Relapsed or refractory lymphoid malignancies (including non-Hodgkin lymphoma,
                  Hodgkin lymphoma and chronic lymphocytic leukemia) meeting the following
                  criteria:

                    -  Disease status: stable disease, partial remission or 2nd and 3rd complete
                       remission

               -  Chronic myelogenous leukemia (CML) in second chronic phase after accelerated or
                  blast crisis; blast crisis defined as:

                    -  Blast count ≥ 20% in the peripheral blood or bone marrow

                    -  Large foci of blasts on bone marrow

                    -  Presence of extra-medullary blastic infiltrate (myeloid sarcoma or chloroma)

               -  Recipients of prior autologous or allogeneic transplant are eligible, as long as
                  at least 3 months have passed since the transplant, and the patient fulfills
                  other eligibility criteria

               -  Eastern Cooperative Oncology Group (ECOG) performance status ≤2

               -  Candidates for reduced intensity conditioning regimens

               -  Patients who do not have human leukocyte antigen (HLA)-matched (defined as
                  matched in HLA A, B, C, and DRB1) related or unrelated donors

               -  Cord Blood Units available through NMDP with the following minimal criteria:

                    -  HLA Match: 4/6 or better match (HLA A, B, DRB1)

                    -  Cell dose: Minimum of 2x107TNC/kg pre thaw

               -  Concurrent therapy for extramedullary leukemia or central nervous system (CNS)
                  lymphoma: concurrent therapy or prophylaxis for testicular leukemia, CNS
                  leukemia, and CNS lymphoma including standard intrathecal chemotherapy and/or
                  radiation therapy will be allowed as clinically indicated; such treatment may
                  continue until the planned course is completed; subjects must be in CNS remission
                  at the time of protocol enrollment if there is a history of CNS involvement

               -  Subjects must have a back-up umbilical cord on the registry in addition to the
                  umbilical cord being used in this study

               -  Subjects must have the ability to understand and the willingness to sign a
                  written informed consent document

        Exclusion Criteria:

          -  Patients with inadequate Organ Function as defined by:

               -  Creatinine clearance < 30 ml/min

               -  Bilirubin ≥ 2 x institutional upper limit of normal

               -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])
                  ≥ 2 x institutional upper limit of normal

               -  Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≥ 2
                  x institutional upper limit of normal

               -  Corrected diffusing capacity of the lung for carbon monoxide (DLCOcorr) < 40%
                  normal

          -  Left ventricular ejection fraction < 35%

          -  Patients with uncontrolled inter-current illness including, but not limited to ongoing
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,
             cardiac arrhythmia, or psychiatric illness/social situations that would limit
             compliance with study requirements

          -  Pregnant or breastfeeding women are excluded from this study
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of patients with BM cellularity failure: Measure of feasibility
Time Frame:42 days after transplant
Safety Issue:
Description:Primary graft failure is defined by <10% BM cellularity in bone marrow biopsies. Failure in more than 30% of patients will indicate unfeasibility of treatment

Secondary Outcome Measures

Measure:Incidence of toxicities assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 12 months
Safety Issue:
Description:Descriptive statistics will be used.
Measure:Rate of neutrophil recovery
Time Frame:Up to 12 months
Safety Issue:
Description:The rate of neutrophil recovery and median time of recovery will be estimated using the methods of Kaplan and Meier.
Measure:Rate of platelet recovery
Time Frame:Up to 12 months
Safety Issue:
Description:The rate of platelet recovery and median time of recovery will be estimated using the methods of Kaplan and Meier.
Measure:Median time of neutrophil recovery
Time Frame:Up to 12 months
Safety Issue:
Description:The median time of neutrophil recovery will be estimated using the methods of Kaplan and Meier.
Measure:Median time of platelet recovery
Time Frame:Up to 12 months
Safety Issue:
Description:The median time of platelet recovery will be estimated using the methods of Kaplan and Meier.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Case Comprehensive Cancer Center

Trial 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

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