Bone marrow transplantation from a donor to a patient who have incompatible blood cells. Before transplantation, patients will receive a less intensive treatment with a low-dose chemiotherapy. The day of transplantation, patients will be injected with a population of blood cells from the donor as well as a specific cell population, named mesenchymal stem cells.

Phase 1

• Conditions: - CML unresponsive/intolerant to Imatinib but not in blast crisis; - CLL; - Non-Hodgkin’s lymphoma (aggressive NHL should have chemosensitive disease); MedDRA version: 14.1Level: PTClassification code 10027703Term: Mismatched donor bone marrow transplantation therapySystem Organ Class: 10042613 - Surgical and medical procedures; - ALL in Complete Remission; - Multiple myeloma not rapidly progressing; Hematological malignancies confirmed histologically and not rapidly progressing: - AML in Complete Remission; - Other myeloproliferative disorders not in blast crisis and not with extensive myelofibrosis; - MDS with < 5% blasts; - Hodgkin’s disease

• Registration Number: EUCTR2009-014980-38-BE
• Lead Sponsor: CHU de Liège

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-01-26
• Last Update Posted: 7 September 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

Patient
1. Hematological malignancies confirmed histologically and not rapidly progressing (see E1.1).
2. Theoretical indication for a standard allo-transplant, but not feasible because: Age > 55 yrs. Unacceptable end organ performance. Patient’s refusal.
3. Indication for a standard auto-transplant: perform mini-allotransplantation 2-6 months after standard autotransplant.
4. Male or female; fertile female patients must use a reliable contraception method;
5. Age < ou = 75 yrs.
6. Informed consent given by patient or his/her guardian if of minor age.
7. One or two HLA mismatches as described in the protocol.

PBSC donors
1. Related to the recipient (sibling, parent or child) or unrelated who hve 1-2 HLA mismatches as either:
- 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.
2. Male or female;
3. Weight > 15 Kg (because of leukapheresis);
4. Fulfills generally accepted criteria for allogeneic PBSC donation;
5. Informed consent given by donor or his/her guardian if of minor age, as per donor center standard procedures.

MSC donors
1. Related to the recipient (sibling, parent or child) or unrelated;
2. Male or female;
3. Age > 16 yrs (no age limit if same as HSC donor);
4. No HLA matching required;
5. Fulfills generally accepted criteria for allogeneic HSC donation;
6. Informed consent given by donor or his/her guardian if of minor age.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patient
1. Any condition not fulfilling inclusion criteria;
2. HIV positive;
3. 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;
4- Uncontrolled infection, arrhythmia or hypertension;
5- Previous radiation therapy precluding the use of 2 Gy TBI;
6- 10/10 HLA-A, -B, -C, DRB1 and DQBI allele-matched donor fit to/willing to donate PBSC.

PBSC donor
1. Any condition not fulfilling inclusion criteria;
2. HIV positive;
3. Unable to undergo leukapheresis because of poor vein access or other reasons.

MSC donor
1. Any condition not fulfilling inclusion criteria;
2. HIV positive;
3. Known allergy to lidocaine;
4. If donor other than HSC donor: any risk factor for transmissible infectious diseases.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The present project aims at evaluating the capacity of mesenchymal stem cells to improve one-year overall survival of patients transplanted with HLA-mismatched peripheral blood stem cells from related or unrelated donors after non-myeloablative conditioning. ;Secondary Objective: Not applicable;Primary end point(s): To compare one-year overall survival between patients treated with MSC or placebo.;Timepoint(s) of evaluation of this end point: One year