Unrelated Umbilical Cord Blood Transplantation With Coinfusion of Mesenchymal Stem Cells

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.

Study Overview

• Status: Completed
• Conditions: Allogeneic Stem Cell Transplantation
• Intervention / Treatment: Other: cord blood transplantation

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)
• 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

  • 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
  • Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) > 3x normal value and/or serum bilirubin >3 mg/dL
  • Cardiac failure (LVEF < 50%)
  • Clinical relevant pulmonary disease: Diffusing capacity of lung for carbon monoxide (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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rik Schots, MD, PhD; Phone Number: +3224763105; Email: Rik.Schots@uzbrussel.be
• Study Contact Backup: Name: Dorien Deneve; Phone Number: +3224776040; Email: Dorien.Deneve@uzbrussel.be

Study Locations

• Belgium
  • Brussel, Belgium, 1090
    • UZ Brussel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 60 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: cord blood transplant; Eligible patients receive cord blood transplantation with coinfusion of mesenchymal stem cells	Other: cord blood transplantation; One or two cord blood transplants with co-infusion of third-party mesenchymal stem cells after pre-transplant preparative regimen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
treatment-related mortality	death related to treatment procedures	day 100 after transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hematopoietic recovery	recovery of peripheral blood counts	One year after transplant

Collaborators and Investigators

• Sponsor: Universitair Ziekenhuis Brussel
• Investigators: Principal Investigator: Rik Schots, MD, PhD, Universitair Ziekenhuis Brussel

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): September 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: March 23, 2010
• First Submitted That Met QC Criteria: March 23, 2010
• First Posted (Estimated): March 24, 2010

Study Record Updates

• Last Update Posted (Estimated): December 6, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: BHS-UCB2009