MSC and HSC Coinfusion in Mismatched Minitransplants

NCT01045382 | Terminated Phase 2

• 1 other identifier: TJB0909
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Leukemia, Myeloid, Acute; Leukemia, Lymphoblastic, Acute; Leukemia, Myelocytic, Chronic; Myeloproliferative Disorders; Myelodysplastic Syndromes; Multiple Myeloma; Leukemia, Lymphocytic, Chronic; Hodgkin's Disease; Lymphoma, Non-Hodgkin

Keywords

HSC transplantation; HLA-mismatched; Mesenchymal stem cells; GVHD; co-infusion

Outcome Measures

Primary Outcomes (1)

• One-year overall survival in the 2 arms.

  One year

Secondary Outcomes (11)

• Incidence of grade II-IV and grade III-IV acute GVDH

  100 days

• Number of absolute donor T cells after HCT in each arm

  28

• Cumulative incidence of non-relapse mortality

  100, 365 and 730 days

• Incidence of extensive chronic GVHD in each arm

  365 days

• Incidence of graft rejection in each arm.

  365 days

Study Arms (2)

Mensenchymal Stem Cells

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Mesenchymal stem cells BIOLOGICAL

Mesenchymal stem cell injection

Mensenchymal Stem Cells

Isotonic solution OTHER

Isotonic solution injection

Placebo

Eligibility Criteria

• Age: Up to 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 HLA-A, -B, -C, DRB1 and DQBI allele-matched donor fit to/willing to donate PBSC.

Sponsors & Collaborators

• University of Liege: lead
• AZ Sint-Jan AV: collaborator
• Ziekenhuis Netwerk Antwerpen (ZNA): collaborator
• Jules Bordet Institute: collaborator
• Universiteit Antwerpen: collaborator
• AZ-VUB: collaborator
• Cliniques universitaires Saint-Luc- Université Catholique de Louvain: collaborator
• University Hospital, Ghent: collaborator

Study Sites (10)

UZA

Edegem, Antwerpen, 2650, Belgium

Location

St-Luc UCL

Brussels, Brabant, 1200, Belgium

Location

AZ Gasthuisberg Leuven

Leuven, Flamish Brabant, 3000, Belgium

Location

UZ Gent

Ghent, Flanders Ost, 9000, Belgium

Location

AZ St-Jan

Bruges, Flanders West, 8000, Belgium

Location

Cliniques Universitaires Mont-Godinne

Yvoir, Namur, 5530, Belgium

Location

Hôpital Stuyvenberg

Antwerp, 2060, Belgium

Location

Bordet Institute

Brussels, 1000, Belgium

Location

Vrije Universiteit Brussel

Brussels, 1050, Belgium

Location

CHU-ULg

Liège, 4000, Belgium

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myeloproliferative Disorders; Myelodysplastic Syndromes; Multiple Myeloma; Leukemia, Lymphocytic, Chronic, B-Cell; Hodgkin Disease; Lymphoma, Non-Hodgkin

Interventions

Isotonic Solutions

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia, B-Cell; Lymphoma

Intervention Hierarchy (Ancestors)

Solutions; Pharmaceutical Preparations

Study Officials

• Yves Beguin, MD, PhD

  CHU-ULg

  PRINCIPAL INVESTIGATOR

• Frédéric Baron, MD, PhD

  CHU-ULg

  STUDY CHAIR

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: January 8, 2010
• First Posted: January 11, 2010
• Study Start: July 1, 2010
• Primary Completion: August 1, 2021
• Study Completion: August 1, 2021
• Last Updated: September 8, 2021

Record last verified: 2021-08

Locations

BE (10)