Mesenchymal Stem Cell Infusion as Prevention for Graft Rejection and Graft-versus-host Disease

Mesenchymal Stem Cell Infusion as Prevention for Graft Rejection and Graft-versus-host Disease After Allogeneic Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning: a Pilot Study

Mesenchymal Stem Cell Infusion as Prevention for Graft Rejection and Graft-Versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning from HLA-mismatched PBSC or cord blood: a Pilot Study

Study Overview

• Status: Completed
• Conditions: Hematological Malignancies
• Intervention / Treatment: Procedure: Mesenchymal stem cell infusion

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Liege, Belgium, 4000
    • CHU Sart Tilman

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

V.1. Patients

V.1.1. Diseases

Hematological malignancies confirmed histologically and not rapidly progressing:

• AML in CR;
• ALL in CR;
• CML unresponsive/intolerant to Imatinib but not in blast crisis;
• Other myeloproliferative disorders not in blast crisis and not with extensive myelofibrosis;
• MDS with < 5% blasts;
• Multiple myeloma;
• CLL;
• Non-Hodgkin's lymphoma (aggressive NHL should have chemosensitive disease);
• Hodgkin's disease.

V.1.2. Clinical situations

• Theoretical indication for a standard allo-transplant, but not feasible because:

  • Age > 55 yrs;
  • Unacceptable end organ performance;
  • Patient's refusal.
• Indication for a standard auto-transplant: perform mini-allotransplantation 2-6 months after standard autotransplant.

V.1.3. Other inclusion criteria

• Male or female; fertile female patients must use a reliable contraception method;
• Age < 75 yrs.
• Informed consent given by patient or his/her guardian if of minor age.

V.1.4. Exclusion criteria

• Any condition not fulfilling inclusion criteria;
• HIV positive;
• Terminal organ failure, except for renal failure (dialysis acceptable);
• Uncontrolled infection, arrhythmia or hypertension;
• Previous radiation therapy precluding the use of 2 Gy TBI;
• HLA-identical donor.

V.2. PBSC donors

V.2.1. Inclusion criteria

• Related to the recipient (sibling, parent or child) or unrelated;
• Male or female;
• Weight > 15 Kg (because of leukapheresis);
• Fulfills generally accepted criteria for allogeneic PBSC donation;
• Informed consent given by donor or his/her guardian if of minor age, as per donor center standard procedures.

V.2.2. Exclusion criteria

• Any condition not fulfilling inclusion criteria;
• HIV positive;
• Unable to undergo leukapheresis because of poor vein access or other reasons.

V.2.3. HLA matching

Related or unrelated donors who have 1-2 HLA mismatches, as either :

• One antigenic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1
• One allelic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1
• Two allelic mismatches at HLA-A or -B or -C or -DRB1 or -DQB1
• One antigenic mismatch + 1 allelic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1.
• One antigenic mismatch at -DQB1 and one other antigenic mismatch at HLA-A or -B or -C or -DRB1

V.3. Cord blood unit

Banked cord blood units will be used if they fulfill the following criteria:

• No more than 2/6 HLA mismatches (antigenic mismatch at HLA-A or HLA-B or allelic mismatch at HLA-DRB1)
• > 2.5 x 107 TNC/kg
• Standard validation by FACT/Netcord criteria.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; MSC co-infusion with either HLA-mismatched PBSC or cord blood	Procedure: Mesenchymal stem cell infusion; Infusion of mesenchymal stem cells on the same day as hematopoietic stem cell infusion.; Other Names: Mesenchymal stem cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Day-100 incidence of non-relapse mortality	100 days

Secondary Outcome Measures

Outcome Measure	Time Frame
1. Hematopoietic engraftment and graft rejection. 2. Incidence of grade II-IV and III-IV acute GVHD. 3. Immunologic reconstitution	365 days

Collaborators and Investigators

• Sponsor: University of Liege
• Investigators: Principal Investigator: Frederic Baron, MD, PhD, CHU-ULg; Principal Investigator: Yves Beguin, MD, PhD, CHU-ULg; Study Chair: Chantal Lechanteur, PhD, CHU-ULg; Study Chair: Etienne Baudoux, MD, CHU-ULg; Study Chair: Evelyne Willems, MD, CHU-ULg

Publications and helpful links

General Publications

• Baron F, Lechanteur C, Willems E, Bruck F, Baudoux E, Seidel L, Vanbellinghen JF, Hafraoui K, Lejeune M, Gothot A, Fillet G, Beguin Y. Cotransplantation of mesenchymal stem cells might prevent death from graft-versus-host disease (GVHD) without abrogating graft-versus-tumor effects after HLA-mismatched allogeneic transplantation following nonmyeloablative conditioning. Biol Blood Marrow Transplant. 2010 Jun;16(6):838-47. doi: 10.1016/j.bbmt.2010.01.011. Epub 2010 Jan 28.

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: July 19, 2007
• First Submitted That Met QC Criteria: July 19, 2007
• First Posted (Estimate): July 20, 2007

Study Record Updates

• Last Update Posted (Estimate): September 2, 2011
• Last Update Submitted That Met QC Criteria: September 1, 2011
• Last Verified: September 1, 2011

More Information

Terms related to this study

• Keywords: HCT, nonmyeloablative, mesenchymal stem cells, GVHD
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms; Graft vs Host Disease
• Other Study ID Numbers: TJB0601