MSC and HSC Coinfusion in Mismatched Minitransplants

Multiple Myeloma Clinical Trial

Official title:

Co-transplantation of Mesenchymal Stem Cells and HLA-mismatched Allogeneic Hematopoietic Cells After Nonmyeloablative Conditioning: a Phase II Randomized Double-blind Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01045382
• Other study ID #: TJB0909
• Status: Terminated
• Phase: Phase 2
• Start date: July 2010
• Est. completion date: August 2021

Study information

• Verified date: August 2021
• Source: University of Liege
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 39
• Est. completion date: August 2021
• Est. primary completion date: August 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Biological:
• Mesenchymal stem cells
Mesenchymal stem cell injection

Other:
• Isotonic solution
Isotonic solution injection

Locations

Country	Name	City	State
Belgium	Hôpital Stuyvenberg	Antwerpen
Belgium	AZ St-Jan	Brugge	Flanders West
Belgium	Bordet Institute	Brussels
Belgium	St-Luc UCL	Brussels	Brabant
Belgium	Vrije Universiteit Brussel	Brussels
Belgium	UZA	Edeghem	Antwerpen
Belgium	UZ Gent	Gent	Flanders Ost
Belgium	AZ Gasthuisberg Leuven	Leuven	Flamish Brabant
Belgium	CHU-ULg	Liège
Belgium	Cliniques Universitaires Mont-Godinne	Yvoir	Namur

Sponsors (8)

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

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	One-year overall survival in the 2 arms.		One year
Secondary	Incidence of grade II-IV and grade III-IV acute GVDH		100 days
Secondary	Number of absolute donor T cells after HCT in each arm		28
Secondary	Cumulative incidence of non-relapse mortality		100, 365 and 730 days
Secondary	Incidence of extensive chronic GVHD in each arm		365 days
Secondary	Incidence of graft rejection in each arm.		365 days
Secondary	Quality and timing of immunologic reconstitution in each arm.		100, 365 and 730 days
Secondary	Detection of MSC from donor origin in recipient marrow after HCT in patients given MSC		40 days
Secondary	Proportion of patients with measurable disease at HCT who achieve a complete response in each arm.		100, 365 and 730 days
Secondary	Cumulative incidence of relapse		365 and 730 days
Secondary	Incidence of progression-free survival		365 and 730 days
Secondary	Incidence of infections		100 days