Adopt immunotherapy in adult patients undergoing hematopoietic stem cell (HSCT) transplantation from a fully compatible donor sibling for the prevention and treatment of GvHD.
Conditions
Interventions
Product Name: ?pa??µe?a HLA-G+ ?-???µ?st??? ??tta?a (iG-Tregs) (Advanced therapy medicinal product
Product Code: iG-Tregs
Pharmaceutical Form: Solution for injection
Sponsors
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Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients 1.Allogeneic Hematopoietic Cell Transplantation (Allo-HCT) from a fully HLA compatible donor sibling. 2. All of the following should be met during the initial evaluation assessment and the day of the iGTreg injection in case the iGTreg injection day is delayed> 14 days after the initial evaluation a) Operating status: Karnofsky = 60% b) Adequate hematopoiesis and organ function, in evaluation of the last 6 weeks: c) Negative pregnancy test within 28 days of inclusion in the study (valid only for women of childbearing potential) AND before iG-Tregs injection 3. Consent to use effective contraception during the transplant period (only applies to sexually active women of childbearing potential and men) 4. Ability to understand and willingness to sign the informed consent form 5. The patient should be on constant prophylaxis of CsA (from day -3) at therapeutic levels (> 200 ng / ml) prior to admission. Donor 1. The donor will be evaluated and meet the requirements according to the procedures of the institution and according to the JACIE standards to undergo leukophase (donor lymphocytes) without stimulation with G-CSF. 2. The donor should have the ability to understand and be willing to sign a written consent upon information specifically for this study. 3. Age 16-75 years 4. Body weight> 40 kg and good general health 5. HLA-fully compatible brother who is also the donor of the participating patient's hematopoietic stem cells 6. Negative pregnancy test (valid only for women of reproductive age) Are the trial subjects under 18? no 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 20 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 6
Exclusion criteria
Exclusion criteria: 1. Grade aGvHD =II (according to the criteria listed in Annex 1) or receiving systemic first-line treatment for the purchase of aGvHD. Stage II of GvHD skin (Grade I) is allowed. 2. Patients with signs of Residual Disease in their last hematological evaluation. 3. Uncontrolled infections that do not respond to treatment. Prophylactic treatment to reactivate CMV or EBV in the absence of evidence of CMV or EBV disease. 4. HBV, HCV or HIV positive individuals 5. Taking any research agent = <28 days before iG Treg injections. Non-indicative agents administered after transplantation (eg valcyte for CMV activation, MMF for GvHD prophylaxis) are allowed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -determine the maximum tolerated dose (MTD) - evaluate the safety of iG-Tregs injection from HLA fully compatible donor after allo-HCT to prevent aGvHD.;Secondary Objective: -to determine the clinical efficacy of iG-Tregs cells in the prevention of aGvHD by allowing the rapid cessation of prophylactic immunosuppression.;Primary end point(s): Determine the safety, tolerance and maximum tolerated dose (MTD) of iG-Treg infusion to prevent GvHD: -Injection-related toxicities for which recipients will be monitored for 1 hour after iGTreg infusion (infusion toxicities classified according to CTCAE v. 4) -Additional toxicities that may occur after iGTreg injections (eg onset or progression of GvHD, infections, relapse). -Toxicities occurring during the first 3 weeks after iG Treg injection will be assessed to assess the safety and tolerability of each specific dose in the dose determination phase (dose-limiting toxicities, DLTs). An iG Treg dose will be considered safe if DLTs occur in only 1/6 or 0/3 members of the cohort during the dosing phase.;Timepoint(s) of evaluation of this end point: Time frame: Up to 90 days after injection | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The clinical efficacy of IG-Treg infusion in the prevention of GvHD: 1. Impact and severity of any GvHD 2. CsA Cessation Day 3. Treatment failure, including occurrence of any GvHD without cessation of CsA no later than day 150 after allo HCT, relapse) 4. Patients receiving iG-Tregs will be compared to another group of patients without infusion and with similar characteristics or historical data.;Timepoint(s) of evaluation of this end point: Time frame: 52 weeks after allo-HCT | — |
Countries
Greece
Contacts
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Outcome results
None listed