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
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
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 Umbilical Cord Blood (UCB) Hematopoietic Stem Cell Transplantation (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 Belgian Hematology Society (BHS) transplant committee will establish a protocol review committee which will organize a central monitoring of the study. Within the context of allogeneic Hematopoietic Stem Cell Transplantation (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.
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
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)
Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 (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)
Mixed lineage leukemia (MLL) rearrangements c)Acute leukemia in second or third remission d)High risk myelodysplastic syndrome: International Prognostic Scoring System (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
T-prolymphocytic leukemia
Chronic lymphocytic 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
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.
Inclusion Criteria:
Exclusion Criteria: