Clinical Trials /

Unrelated Umbilical Cord Blood Transplantation With Coinfusion of Mesenchymal Stem Cells

NCT01092026

Description:

A pilot study to assess the feasibility of unrelated umbilical cord blood transplantation with coinfusion of third-party mesenchymal stem cells after myeloablative or nonmyeloablative conditioning in patients with hematological malignancies. This is a multicenter single arm, phase I-II pilot study. The primary objective of this study is to determine the feasibility of UCB HSCT with co-infusion of third party mesenchymal stem cells as assessed by the treatment-related mortality at d100 after transplant. Patient inclusion criteria: Age 15-60 yrs Patients for whom allogeneic stem cell transplantation is the preferred treatment option, with the following hematological malignancies:acute myeloid leukemia, acute lymphoblastic leukemia, high risk myelodysplastic syndrome, advanced lymphoproliferative disorders, chronic myeloid leukemia (refractory or intolerant to second-line tyrosine kinase inhibitors), multiple myeloma Informed consent given Patient exclusion criteria Previous allogeneic transplant Progressive malignant disease Significant organ damage as a contraindication to allotransplantation Significant psychiatric or neurological disorder Uncontrolled viral, fungal or bacterial infection Pregnancy HIV positive Patients will receive either myeloablative or reduced intensity conditioning. One or 2 cord blood transplants will be transplanted, followed by infusion of a third-party mesenchymal stem cell transplant Adverse event reporting BHS transplant committee will establish a protocol review committee which will organize a central monitoring of the study. Within the context of allogeneic HSCTx many severe events are likely to occur. Statistics and stopping rules The trial will be stopped at any time that there is reasonable evidence that the true rate of day +100 nonrelapse mortality exceeds 0.40. It is the intention to include an initial 20 patients.

Related Conditions:
  • Acute Erythroid Leukemia
  • Acute Leukemia
  • Acute Lymphoblastic Leukemia
  • Acute Megakaryoblastic Leukemia
  • Acute Myeloid Leukemia
  • B-Cell Prolymphocytic Leukemia
  • Chronic Lymphocytic Leukemia
  • Chronic Myeloid Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Mantle Cell Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Secondary Acute Myeloid Leukemia
  • T-Cell Prolymphocytic Leukemia
Recruiting Status:

Unknown status

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Unrelated Umbilical Cord Blood Transplantation With Coinfusion of Mesenchymal Stem Cells
  • Official Title: A Pilot Study to Assess the Feasibility of Unrelated Umbilical Cord Blood Transplantation With Coinfusion of Third-party Mesenchymal Stem Cells After Myeloablative or Nonmyeloablative Conditioning in Patients With Hematological Malignancies

Clinical Trial IDs

  • ORG STUDY ID: BHS-UCB2009
  • NCT ID: NCT01092026

Conditions

  • Allogeneic Stem Cell Transplantation

Purpose

A pilot study to assess the feasibility of unrelated umbilical cord blood transplantation with coinfusion of third-party mesenchymal stem cells after myeloablative or nonmyeloablative conditioning in patients with hematological malignancies. This is a multicenter single arm, phase I-II pilot study. The primary objective of this study is to determine the feasibility of UCB HSCT with co-infusion of third party mesenchymal stem cells as assessed by the treatment-related mortality at d100 after transplant. Patient inclusion criteria: Age 15-60 yrs Patients for whom allogeneic stem cell transplantation is the preferred treatment option, with the following hematological malignancies:acute myeloid leukemia, acute lymphoblastic leukemia, high risk myelodysplastic syndrome, advanced lymphoproliferative disorders, chronic myeloid leukemia (refractory or intolerant to second-line tyrosine kinase inhibitors), multiple myeloma Informed consent given Patient exclusion criteria Previous allogeneic transplant Progressive malignant disease Significant organ damage as a contraindication to allotransplantation Significant psychiatric or neurological disorder Uncontrolled viral, fungal or bacterial infection Pregnancy HIV positive Patients will receive either myeloablative or reduced intensity conditioning. One or 2 cord blood transplants will be transplanted, followed by infusion of a third-party mesenchymal stem cell transplant Adverse event reporting BHS transplant committee will establish a protocol review committee which will organize a central monitoring of the study. Within the context of allogeneic HSCTx many severe events are likely to occur. Statistics and stopping rules The trial will be stopped at any time that there is reasonable evidence that the true rate of day +100 nonrelapse mortality exceeds 0.40. It is the intention to include an initial 20 patients.

Detailed Description

      PROTOCOL SYNOPSIS

      Title of the study A pilot study to assess the feasibility of unrelated umbilical cord blood
      transplantation with coinfusion of third-party mesenchymal stem cells after myeloablative or
      nonmyeloablative conditioning in patients with hematological malignancies.

      Design of the study This is a multicenter single arm, phase I-II pilot study.

      Primary objective The primary objective of this study is to determine the feasibility of UCB
      HSCT with co-infusion of third party mesenchymal stem cells as assessed by the
      treatment-related mortality at d100 after transplant.

      Secondary objectives

        -  Chimerism at multiple time points

        -  Hematopoietic recovery (neutrophil and platelet engraftment)

        -  Immune recovery

        -  Incidence of acute and chronic graft-versus-host disease (GVHD)

        -  Infectious complications

        -  Disease free survival

        -  Relapse incidence

        -  Overall survival

      Graft criteria

        -  No peripheral blood or marrow donor available at the 9/10 compatibility level using high
           resolution typing techniques

        -  Adequate cord blood transplant available:

           a)Single cord blood

        -  Minimal 4/6 match (DR1-high, A-low, B-low)

        -  Minimal 2 (6/6), 2.5 (5/6) or 3 (4/6) x 10exp7 nucleated cells per kg in the graft
           b)Double cord blood

        -  At least 4/6 common antigens shared by recipient and the 2 cord blood transplants

        -  Minimal 3x 10exp7 nucleated cells per kg in the combined graft

      Patient inclusion criteria

        -  Age 15-60 yrs

        -  Allogeneic stem cell transplantation is the preferred treatment option:

           a)High risk acute myeloid leukemia (AML) in first complete remission (CR)

        -  Preceding myelodysplastic syndrome

        -  High risk karyotypes (e.g. monosomy 5 or 7, complex)

        -  FLT3 alteration

        -  > 2 cycles to obtain CR

        -  Erythroblastic or megakaryocytic leukemia b)High risk acute lymphoblastic leukemia (ALL)
           in first CR

        -  High risk karyotypes (e.g. t[9;22], t[4;11], t[1;19], complex)

        -  MLL rearrangements c)Acute leukemia in second or third remission d)High risk
           myelodysplastic syndrome: IPSS Intermediate-2 or high risk e)Advanced
           lymphoproliferative disorders

        -  Diffuse large B-cel non-Hodgkin lymphoma (NHL) or mantle cell NHL or B-prolymphocytic
           leukemia

             -  Sensitive relapse after autologous HSCTx

        -  T-prolymphocytic leukemia

        -  Chronic lymphocytic leukemia

             -  Refractory to fludarabine

             -  Adverse karyotypes (del p17) f)Chronic myeloid leukemia

        -  Refractory or intolerant to second-line tyrosine kinase inhibitors g)Multiple myeloma

        -  Advanced disease (selected cases)

        -  Informed consent given

      Patient exclusion criteria

        -  Previous allogeneic transplant

        -  Progressive malignant disease

        -  Significant organ damage as a contraindication to allotransplantation

             -  Creatinine clearance < 60 ml/min

             -  AST/ALT > 3x normal value and/or serum bilirubin >3 mg/dL

             -  Cardiac failure (LVEF < 50%)

             -  Clinical relevant pulmonary disease: DLCO < 50% normal

        -  Significant psychiatric or neurological disorder

        -  Uncontrolled viral, fungal or bacterial infection

        -  Pregnancy

        -  HIV positive

      Study procedure Patients will receive either myeloablative or reduced intensity conditioning.
      One or 2 cord blood transplants will be transplanted, followed by infusion of a third-party
      mesenchymal stem cell transplant

      Adverse event reporting BHS transplant committee will establish a protocol review committee
      which will organize a central monitoring of the study. Within the context of allogeneic HSCTx
      many severe events are likely to occur.

      Statistics and stopping rules The trial will be stopped at any time that there is reasonable
      evidence that the true rate of day +100 nonrelapse mortality exceeds 0.40. It is the
      intention to include an initial 20 patients.
    

Trial Arms

NameTypeDescriptionInterventions
cord blood transplantExperimentalEiligible patients receive cord blood transplantation with coinfusion of mesenchymal stem cells

    Eligibility Criteria

            Inclusion Criteria:
    
              -  Allogeneic stem cell transplantation is the preferred treatment option:
    
              -  High risk acute myeloid leukemia (AML) in first complete remission (CR)
    
              -  Preceding myelodysplastic syndrome
    
              -  High risk karyotypes (e.g. monosomy 5 or 7, complex)
    
              -  FLT3 alteration
    
              -  > 2 cycles to obtain CR
    
              -  Erythroblastic or megakaryocytic leukemia
    
              -  High risk acute lymphoblastic leukemia (ALL) in first CR
    
              -  High risk karyotypes (e.g. t[9;22], t[4;11], t[1;19], complex)
    
              -  MLL rearrangements
    
              -  Acute leukemia in second or third remission
    
              -  High risk myelodysplastic syndrome: IPSS Intermediate-2 or high risk
    
              -  Advanced lymphoproliferative disorders
    
              -  Diffuse large B-cel non-Hodgkin lymphoma (NHL) or mantle cell NHL or
    
              -  B-prolymphocytic leukemia
    
              -  Sensitive relapse after autologous HSCTx
    
              -  T-prolymphocytic leukemia
    
              -  Chronic lymphocytic leukemia
    
              -  Refractory to fludarabine
    
              -  Adverse karyotypes (del p17)
    
              -  Chronic myeloid leukemia
    
              -  Refractory or intolerant to second-line tyrosine kinase inhibitors
    
              -  Multiple myeloma
    
              -  Advanced disease (selected cases)
    
              -  Informed consent given
    
            Exclusion Criteria:
    
              -  Previous allogeneic transplant
    
              -  Progressive malignant disease
    
              -  Significant organ damage as a contraindication to allotransplantation
    
              -  Creatinine clearance < 60 ml/min
    
              -  AST/ALT > 3x normal value and/or serum bilirubin > 3 mg/dL
    
              -  Cardiac failure (LVEF < 50%)
    
              -  Clinical relevant pulmonary disease: DLCO < 50% normal
    
              -  Significant psychiatric or neurological disorder
    
              -  Uncontrolled viral, fungal or bacterial infection
    
              -  Pregnancy
    
              -  HIV positive
          
    Maximum Eligible Age:60 Years
    Minimum Eligible Age:15 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:treatment-related mortality
    Time Frame:day 100 after transplant
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Hematopoietic recovery
    Time Frame:One year after transplant
    Safety Issue:
    Description:

    Details

    Phase:Phase 1/Phase 2
    Primary Purpose:Interventional
    Overall Status:Unknown status
    Lead Sponsor:Universitair Ziekenhuis Brussel

    Last Updated

    June 3, 2016