MSC and HSC Coinfusion in Mismatched Minitransplants

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by University Hospital of Liege
Sponsor:
Collaborators:
AZ Sint-Jan AV
Ziekenhuis Netwerk Antwerpen (ZNA)
Jules Bordet Institute
Universiteit Antwerpen
Katholieke Universiteit Leuven
AZ-VUB
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
University Hospital, Ghent
University Hospital of Mont-Godinne
Queen Fabiola Children's University Hospital
Information provided by (Responsible Party):
Yves Beguin, University Hospital of Liege
ClinicalTrials.gov Identifier:
NCT01045382
First received: January 8, 2010
Last updated: January 17, 2013
Last verified: January 2013
  Purpose

The present project aims at evaluating the capacity of MSC to improve one-year overall survival of patients transplanted with HLA-mismatched PBSC from related or unrelated donors after non-myeloablative conditioning.

Co-infusion of MSC has been shown to facilitate engraftment of hematopoietic stem cell (HSC) in an immunodeficient mouse model. In addition, it has been shown that infusion of third party MSC in HSC transplantation could be successfully used as treatment for grade II-IV steroid-refractory acute graft versus host disease.

One hundred and twenty patients with HLA-mismatched donors will be included over 6 years at multiple centers across Belgium through the transplant committee of the Belgian Hematological Society. The conditioning regimen will consist of fludarabine and 2 Gy TBI, followed by the infusion of donor HSC. Patients will be randomized 1/1 in double-blind fashion to receive or not MSC (1.5-.3.0 x106/kg) from third-party (either haploidentical family members or unrelated volunteer) donors on day 0. Postgrafting immunosuppression will combine tacrolimus and MMF. Except for the collection, expansion and infusion of MSC, the clinical management of the patient will not differ from that of routine NM-HCT.


Condition Intervention Phase
Leukemia, Myeloid, Acute
Leukemia, Lymphoblastic, Acute
Leukemia, Myelocytic, Chronic
Myeloproliferative Disorders
Myelodysplastic Syndromes
Multiple Myeloma
Leukemia, Lymphocytic, Chronic
Hodgkin's Disease
Lymphoma, Non-Hodgkin
Biological: Mesenchymal stem cells
Other: Isotonic solution
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
Official Title: Co-transplantation of Mesenchymal Stem Cells and HLA-mismatched Allogeneic Hematopoietic Cells After Nonmyeloablative Conditioning: a Phase II Randomized Double-blind Study

Resource links provided by NLM:


Further study details as provided by University Hospital of Liege:

Primary Outcome Measures:
  • One-year overall survival in the 2 arms. [ Time Frame: One year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of grade II-IV and grade III-IV acute GVDH [ Time Frame: 100 days ] [ Designated as safety issue: No ]
  • Number of absolute donor T cells after HCT in each arm [ Time Frame: 28 ] [ Designated as safety issue: No ]
  • Cumulative incidence of non-relapse mortality [ Time Frame: 100, 365 and 730 days ] [ Designated as safety issue: Yes ]
  • Incidence of extensive chronic GVHD in each arm [ Time Frame: 365 days ] [ Designated as safety issue: No ]
  • Incidence of graft rejection in each arm. [ Time Frame: 365 days ] [ Designated as safety issue: No ]
  • Quality and timing of immunologic reconstitution in each arm. [ Time Frame: 100, 365 and 730 days ] [ Designated as safety issue: No ]
  • Detection of MSC from donor origin in recipient marrow after HCT in patients given MSC [ Time Frame: 40 days ] [ Designated as safety issue: No ]
  • Proportion of patients with measurable disease at HCT who achieve a complete response in each arm. [ Time Frame: 100, 365 and 730 days ] [ Designated as safety issue: Yes ]
  • Cumulative incidence of relapse [ Time Frame: 365 and 730 days ] [ Designated as safety issue: Yes ]
  • Incidence of progression-free survival [ Time Frame: 365 and 730 days ] [ Designated as safety issue: No ]
  • Incidence of infections [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 120
Study Start Date: July 2010
Estimated Study Completion Date: July 2018
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mensenchymal Stem Cells

Efficacy of MSC infusion on one-year overall survival of patients transplanted with HLA-mismatched PBSC.

Patients will receive a conditioning regimen consisting in fludarabine (total dose 90 mg/square meter) and 2 Gy total body irradiation.

MSC cells (1,5-3,0 x 10E6 MSC/Kg BW) will be injected, followed, at least one hour later, by the infusion of HLA-mismatched PBSC from related or unrelated donor.

Biological: Mesenchymal stem cells
Mesenchymal stem cell injection
Placebo Comparator: Placebo

Patients will receive a conditioning regimen consisting in fludarabine (total dose 90 mg/square meter) and 2Gy total body irradiation.

Isotonic solution will be injected will be injected, followed, at least one hour later, by the infusion of HLA-mismatched PBSC from related or unrelated donor.

Other: Isotonic solution
Isotonic solution injection

  Eligibility

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • Male or female; fertile female patients must use a reliable contraception method
  • Age ≤ 75 year old
  • Informed consent given by patient or his/her guardian if of minor age.
  • One or two HLA mismatches with PBSC:

    • One antigenic 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
    • Patients with one single allelic mismatch at HLA-A or -B or -C or -DRB1 or -DQB1 can also be included in the protocol.
  • Hematological malignancies confirmed histologically and not rapidly progressing:

    • AML in complete remission
    • ALL in complete remission
    • 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 not rapidly progressing
    • CLL
    • Non-Hodgkin's lymphoma (aggressive NHL should be chemosensitive)
    • Hodgkin's disease

Exclusion Criteria:

  • Any condition not fulfilling inclusion criteria
  • HIV positive
  • Terminal organ failure, except for renal failure (dialysis acceptable)

    • Cardiac: Symptomatic coronary artery disease or other cardiac failure requiring therapy; ejection fraction <35%; uncontrolled arrhythmia; uncontrolled hypertension
    • Pulmonary: DLCO < 35% and/or receiving supplementary continuous oxygen
    • Hepatic: Fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease
  • Uncontrolled infection, arrhythmia or hypertension
  • Previous radiation therapy precluding the use of 2 Gy TBI
  • 10/10 HLA-A, -B, -C, DRB1 and DQBI allele-matched donor fit to/willing to donate PBSC.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01045382

Contacts
Contact: Yves Beguin, MD, PhD 00/32/4 366 7201 yves.beguin@chu.ulg.ac.be
Contact: Frédéric Baron, MD, PhD 00/32/4 366 7201 F.Baron@ulg.ac.be

Locations
Belgium
UZA Recruiting
Edeghem, Antwerpen, Belgium, 2650
Contact: Wilfried Schroyens, MD, PhD    32 382 204111    wilfried.schroyens@uza.be   
Principal Investigator: Wilfried Schroyens, MD, PhD         
St-Luc UCL Recruiting
Brussels, Brabant, Belgium, 1200
Contact: Augustin Ferrant, MD, PhD    32 27641880    ferrant@sang.ul.ac.be   
Principal Investigator: Augustin Ferrant, MD, PhD         
AZ Gasthuisberg Leuven Recruiting
Leuven, Flamish Brabant, Belgium, 3000
Contact: Johan Maertens, MD    32- 16 33 22 11    johan.maertens@uz.kuleuven.ac.be   
Principal Investigator: Johan Maertens, MD         
UZ Gent Recruiting
Gent, Flanders Ost, Belgium, 9000
Contact: Lucien Noens, MD, PhD    32(09) 332 21 31    Lucien.Noens@Ugent.be   
Principal Investigator: Lucien Noens, MD, PhD         
Sub-Investigator: Tessa Kerre, MD, PhD         
AZ St-Jan Recruiting
Brugge, Flanders West, Belgium, 8000
Contact: Dominik Selleslag, MD    00/32/50 453060    dominik.selleslag@azbrugge.be   
Principal Investigator: Dominik Selleslag, MD         
Cliniques Universitaires Mont-Godinne Recruiting
Yvoir, Namur, Belgium, 5530
Contact: Carlos Graux, MD    32(081)423831    carlos.graux@uclouvain.be   
Contact: Chantal Doyen, MD    32(081)423831    chantal.doyen@sang.ucl.ac.be   
Principal Investigator: Chantal Doyen, MD, PhD         
Sub-Investigator: Carlos Graux, MD, PhD         
Hôpital Stuyvenberg Recruiting
Antwerpen, Belgium, 2060
Contact: Pierre Zachée, MD, PhD    32(03)2177111    pierre.zachee@zna.be   
Principal Investigator: Pierre Zachée, MD, PhD         
Bordet Institute Recruiting
Brussels, Belgium, 1000
Contact: Philippe Lewalle, MD, PhD    00/32/2 5417208    plewalle@ulb.ac.be   
Contact: Dominique Bron, MD, PhD    00/32/ 2 5417208    bron@ulb.ac.be   
Principal Investigator: Philippe Lewalle, MD, PhD         
Sub-Investigator: Dominique Bron, MD, PhD         
Vrije Universiteit Brussel Recruiting
Brussels, Belgium, 1050
Contact: Rik Schots, MD    00/32/2 4763105    Rik.Schots@uzbrussel.be   
Principal Investigator: Rik Schots, MD         
CHU-ULg Recruiting
Liège, Belgium, 4000
Contact: Yves Beguin, MD, PhD    00/32/4 3667201    yves.beguin@chu.ulg.ac.be   
Contact: Frédéric Baron, MD, PhD    00/32/4 3667201    F.Baron@chu.ulg.ac.be   
Principal Investigator: Yves Beguin, MD, PhD         
Sub-Investigator: Frédéric Baron, MD, PhD         
Sub-Investigator: Chantal Lechanteur, PhD         
Sub-Investigator: Etienne Baudoux, MD         
Sub-Investigator: Evelyne Willems, MD         
Sponsors and Collaborators
University Hospital of Liege
AZ Sint-Jan AV
Ziekenhuis Netwerk Antwerpen (ZNA)
Jules Bordet Institute
Universiteit Antwerpen
Katholieke Universiteit Leuven
AZ-VUB
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
University Hospital, Ghent
University Hospital of Mont-Godinne
Queen Fabiola Children's University Hospital
Investigators
Principal Investigator: Yves Beguin, MD, PhD CHU-ULg
Study Chair: Frédéric Baron, MD, PhD CHU-ULg
Principal Investigator: Evelyne Willems, MD CHU-ULg
Principal Investigator: Dominik Selleslag, MD, PhD AZ Brugge
Principal Investigator: Pierre Zachée, MD, PhD ZNA Antwerpen
Principal Investigator: Philippe Lewalle, MD, PhD Bordet Institute, Brussels
Principal Investigator: Dominique Bron, MD, PhD Bordet Institute, Brussels
Principal Investigator: Wilfried Schroyens, MD, PhD UZA Antwerpen
Principal Investigator: Chantal Lechanteur, PhD CHU-ULg
Principal Investigator: Etienne Baudoux, MD CHU-ULg
Principal Investigator: Johan Maertens, MD KUL, Leuven
Principal Investigator: Rik Schots, MD, PhD AZ VUB, Brussels
Principal Investigator: Augustin Ferrant, MD, PhD UCL St. LUC, Brussels
Principal Investigator: Lucien Noens, MD, PhD UZG Gent
Principal Investigator: Chantal Doyen, MD, PhD Cliiques Universitaire Mont-Godinne, Yvoir
Principal Investigator: Tessa Kerre, MD, PhD UZA, Antwerpen
Principal Investigator: Carlos Graux, MD, PhD Cliniques Universitaires, Mont-Godinne
  More Information

No publications provided

Responsible Party: Yves Beguin, Prof, University Hospital of Liege
ClinicalTrials.gov Identifier: NCT01045382     History of Changes
Other Study ID Numbers: TJB0909
Study First Received: January 8, 2010
Last Updated: January 17, 2013
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products

Keywords provided by University Hospital of Liege:
HSC transplantation
HLA-mismatched
Mesenchymal stem cells
GVHD
co-infusion

Additional relevant MeSH terms:
Hodgkin Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma
Lymphoma, Non-Hodgkin
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Bone Marrow Diseases
Hematologic Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on July 31, 2014