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Unrelated Umbilical Cord Blood Transplantation With Coinfusion of Mesenchymal Stem Cells

Sponsor
Universitair Ziekenhuis Brussel (Other)
Overall Status
Unknown status
CT.gov ID
NCT01092026
Collaborator
(none)
20
Enrollment
1
Location
1
Arm
85
Duration (Months)
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Other: cord blood transplantation
 Phase 1/Phase 2

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Study Start Date :
Nov 1, 2010
Anticipated Primary Completion Date :
Dec 1, 2017
Anticipated Study Completion Date :
Dec 1, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: cord blood transplant

Eiligible 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

Outcome Measures

Primary Outcome Measures

  1. treatment-related mortality [day 100 after transplant]

Secondary Outcome Measures

  1. Hematopoietic recovery [One year after transplant]

Eligibility Criteria

Criteria

Ages Eligible for Study:
15 Years to 60 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 UZ Brussel Brussel Belgium 1090

Sponsors and Collaborators

  • Universitair Ziekenhuis Brussel

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Universitair Ziekenhuis Brussel
ClinicalTrials.gov Identifier:
NCT01092026
Other Study ID Numbers:
  • BHS-UCB2009
First Posted:
Mar 24, 2010
Last Update Posted:
Jun 6, 2016
Last Verified:
May 1, 2016

Study Results

No Results Posted as of Jun 6, 2016