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

January 8, 2010
January 17, 2013
July 2010
July 2016   (final data collection date for primary outcome measure)
One-year overall survival in the 2 arms. [ Time Frame: One year ] [ Designated as safety issue: No ]
To compare one-year overall survival in the 2 arms. [ Time Frame: One year ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01045382 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 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 ]
  • To evaluate the 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 ]
Not Provided
Not Provided
 
MSC and HSC Coinfusion in Mismatched Minitransplants
Co-transplantation of Mesenchymal Stem Cells and HLA-mismatched Allogeneic Hematopoietic Cells After Nonmyeloablative Conditioning: a Phase II Randomized Double-blind Study

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Treatment
  • 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
    Mesenchymal stem cell injection
  • Other: Isotonic solution
    Isotonic solution injection
  • 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.

    Intervention: Biological: Mesenchymal stem cells
  • 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.

    Intervention: Other: Isotonic solution
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
120
July 2018
July 2016   (final data collection date for primary outcome measure)

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.
Both
up to 75 Years
No
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
Belgium
 
NCT01045382
TJB0909
No
Yves Beguin, University Hospital of Liege
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
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
University Hospital of Liege
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP