Hematological disorders of the following types: ALL: acute lymphoblastic leukemia in complete remission (<5% blasts in marrow) up to and including third remission (excluding relapse). AML: acute myelocytic leukemia in remission (excluding relapse). CML: chronic myelocytic leukemia who are in the chronic phase of the disease. Severe aplastic anemia, hemoglobinopathies (thalassemia major). Inborn errors of metabolism. Myelodysplastic syndromes MedDRA version: 9.1 Level: LLT Classification code 10
Conditions
Interventions
Product Name: Mesenchymal stem cells
Product Code: MSC
Pharmaceutical Form: Intravenous infusion
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intr
Sponsors
CHU Sart-Tilman
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patient inclusion criteria 1. Informed consent. 2. Patients/subjects are required to meet the following inclusion criteria: a. Hematological disorders of the following types: ALL: patients with acute lymphoblastic leukemia in CR (50% of predicted and DLCO >50% of predicted. 5. Female patients are non-pregnant. 6 Patients must be HIV-1 and –2 antibody, HIV -1 antigen and hepatite A, B and C seronegatives. 7. Patients must have a Karnofsky score of =70. 8. Patients must have an HLA-A, -B and -DRß1 identical stem cell donor. (HLA typing according to the routine at each center). 9. Immunosuppression should consist of cyclosporine or tacrolimus combined with four doses of methotrexate. Methotrexate is given on day+1, 15 mg/m2 and 10 mg/m2 on days +3, +6 and +11 after transplantation. Cyclosporine or tacromilus dose is according to the routines at each center. Because acute GvHD is a primary endpoint, no other immunosuppression than cyclosporine combined with methotrexate will be allowed. Donor inclusion criteria 1. MSC donor must be HIV, HB-s antigen, anti HBc and anti HCV negative. 2. Related haploidentical or HLA mismatched MSC donor willing to donate MSC 3. Signed informed consent. 4. Each center request either bone marrow or peripheral blood stem cells according to routine at each center. If the donor only accepts one type of donation, he/she may be included anyhow. 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
Exclusion criteria: Patient exclusion criteria 1. Hematologic malignancies, of the following types a) ALL patients in relapse as defined by >5% blasts in the marrow and/or circulating blasts in the peripheral blood, b) AML patients in relapse as defined by >5% blasts in the marrow. c) AML/ALL CR4 or later. d) CML in accelerated phase or blast crisis. e) MDS > RAEB II. 2. Patient has active alcohol or substance abuse. 3. Patient has a medical condition, which, in the opinion of the clinical investigator, would interfere with the evaluation of the patient. 4. Patient needing hematopoietic stem cell transplantation within three weeks. 5. Patient with a history of hyper-sensitivity to penicillin Donor exclusion criteria 1. Donor more than 65 years of age, or unhealthy. 2. Donor positive for HIV, HTLV, hepatitis Bs antigen, anti-HCV or anti- HBc.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of this study is to evaluate the functioning of mesenchymal stem cells (MSC) in supporting hematopoietic cells transplantation (HSC). Cotransplantation of MSC with HSC may be beneficial by preventing rejection, decreasing graft-versus-host disease, enhancing engraftment and preventing tissue toxicity by chemoirradiation. GvDH incidence (acute grade II-IV GvDH) will be used as measure of efficacy. ;Secondary Objective: 1. Determination of time to neutrophil engraftment (>0.5 x 10E9/l). 2. Determination of time to platelet engraftment (>30 x 10E9/l). 3. Platelet level at day 30 post transplant. 4. Transfusions during first 30 days. 5. Incidence of chronic GvHD. 6. Treatment-related mortality (causes of death). 7. Overall relapse rate. 8. Survival. 9. Disease-free survival.;Primary end point(s): To establish the efficacy of infusions of identical, haploidentical or mismatched related or unrelated MSC in matched unrelated donor allogeneic hematopoietic stem cell transplantation of patients with hematologic malignancies and inborn errors of metabolism. GvHD incidence (acute grade II-IV GvDH) will be used as measure of efficacy. | — |
Countries
Belgium
Outcome results
None listed