Hematologic Malignancies
Conditions
Brief summary
MESENCHYMAL STROMAL CELLS (MSC) have shown promising albeit not always consistent therapeutic effects in the treatment of severe steroid-resistant acute Graf versus Host Disease. Remarkably, in all reported clinical studies the toxicity of Mesenchymal stromal cells administration has been found consistently negligible. The investigators believe that Umbilical Cord (UC) derived Mesenchymal stromal cells may represent a stronger immunosuppressive tool for such clinical emergency and no data suggest any change in the safety profile of these cells. For this reason, and in the best interest of the patient, the investigators plan to test the safety and activity of Umbilical Cord Mesenchymal stromal cells when given sequentially to another partially effective treatment of steroid resistant acute graf versus host disease such as Pentostatin.
Interventions
BIOLOGICALUMBILICAL CORD DERIVED MESENCHYMAL STROMAL CELLS (UC-MSC)
pentostatin, dose 1 mg/m2 § MSC doses: 1. 3 patients → 3 infusions of 1x106 cells /kg 2. 3 patients → 3 infusions of 2x106 cells /kg 3. 3 patients → 3 infusions of 3x106 cells /kg
Sponsors
Associazione Italiana per la Ricerca sul Cancro
A.O. Ospedale Papa Giovanni XXIII
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 70 Years
Healthy volunteers
No
Inclusion criteria
Patients are required to meet the following inclusion criteria: 1. Patients with steroid refractory grade III-IV classic acute graft versus host disease (GvHD)occurring within 100 days after transplant or induced by donor lymphocyte infusions (DLI) or T-cell add back. Steroid refractory graft versus host disease (GvHD)is defined according to Pidala and Anasetti10 as follows: a) progression of at least 1 overall grade within 3 days of optimal steroid treatment; b) failure to demonstrate any overall grade improvement over 5 to 7 days; c) incomplete response by 14 days of 2 mg/kg/day of steroid therapy. 2. Patients with persistent, recurrent, or late acute graft versus host disease (GvHD) (features of acute graft versus host disease occurring beyond 100 days, often during withdrawal of immune suppression). 3. Patients with an overlap syndrome in which diagnostic or distinctive features of chronic graft versus host disease (GvHD) and acute graft versus host disease (GvHD) appear together79.
Exclusion criteria
1\. Inability to obtain written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| vital parameters | one year | Following infusion of UC-MSC, the patient will be monitored for acute infusion-related toxicity. Any toxicity will be treated at the discretion of the attending physician. Infusional toxicity is defined as any alteration of the vital parameters of the patient if they have appeared acutely and may be directly correlated to the UC-MSC infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| assessed of acute graft versus host disease (GvHD) | one year | graft versus host disease will be assessed at day +7, +9, +12, +14, +16, +19, +21, +28, + 35, +42 e +49 and after 6 months and 1 year from the last UC-MSC infusion. Efficacy on acute graft versus host disease is defined as complete or partial resolution of acute GvHD evaluated according to conventional staging and grading score systems.The efficacy will be evaluated at day +30 after the third UC-MSC infusion or, if less, at day +30 after the last UC-MSC infusion. |
Countries
Italy
Contacts
Primary ContactALESSANDRO RAMBALDI, MD
Outcome results
None listed