IG-TREGS for Graft-versus-host disease (GvHD)|Allogeneic haematopoietic stem cell transplantation

Inclusion criteria

• {"criterion_text":"- Patient inclusion criteria: 1. Male or female patients aged 18–75 years on the day of informed consent, who have undergone allogeneic hematopoietic cell transplantation (Allo-HCT) from a fully HLA-matched sibling donor. Note: For patients >75 years, transplant eligibility will be assessed after discussion between the Investigator and the patient’s treating physician.\n- Donor inclusion criteria: 5. HLA-matched sibling donor of the patient’s hematopoietic stem cells\n- Donor inclusion criteria: 6. For WOCBP, negative serum pregnancy test at screening (Day +28) and negative urine pregnancy test before leukapheresis/blood collection (Day +35)\n- Patient inclusion criteria: 2. All of the following must be met at initial eligibility assessment and on the day of iG-Treg infusion if the infusion is delayed >14 days from initial assessment: a) Performance status: Karnofsky ≥ 60% b) Adequate hematopoietic and organ function (assessed within last 6 weeks): o\tAbsolute neutrophil count (ANC) >1 x 10^9/L o\tSerum creatinine ≤2 mg/dL or GFR >40 mL/min/1.73 m² o\tAST or ALT <3 x upper limit of normal (ULN) o\tTotal bilirubin ≤2.5 mg/dL (not applied to participants with Gilbert’s syndrome) o\tAlbumin >2.5 g/dL o\tOxygen saturation ≥92% on room air o\tChest X-ray or CT scan without signs of infection o\tNo significant cardiac disease and/or left ventricular ejection fraction >35% on echocardiogram\n- Patient inclusion criteria: 3. Women of Childbearing Potential (WOCBP): Negative serum pregnancy test within 28 days before study entry Negative urine pregnancy test at eligibility confirmation (Day +56) and prior to iG-Treg infusion (Day +63) Agreement to use a highly effective method of contraception throughout the study and for ≥3 months after last IMP administration Highly effective contraception methods include: Hormonal contraception (combined or progestin-only, oral, injectable, transdermal, or implantable) Intrauterine device (IUD) or intrauterine system (IUS) Bilateral tubal occlusion Permanent sexual abstinence, if consistent with lifestyle / Women Not of Childbearing Potential (WONCBP): Eligible without requirement for pregnancy testing or contraception Defined as women who are surgically sterile (hysterectomy, bilateral oophorectomy, and/or bilateral salpingectomy) or postmenopausal (≥12 consecutive months of amenorrhea without alternative medical cause) / Male Participants: Must use condoms (with or without spermicide) during study and for ≥3 months after IMP administration Must ensure female partner uses highly effective contraception for the same period Sperm donation is prohibited during study and for same period post-study\n- Patient inclusion criteria: 4. Ability to understand and willingness to sign the approved informed consent form after explanation\n- Patient inclusion criteria: 5. Patient must be on continuous GvHD prophylaxis with cyclosporine (CsA) at therapeutic levels (>200 ng/mL) from Day -3 pre-transplant up to before study inclusion\n- Donor inclusion criteria: 1. If donor undergoes leukapheresis (for collection of donor lymphocytes), they must meet standards according to institutional SOPs and FACT-JACIE donor selection criteria; leukapheresis of therapeutic cells must be performed without G-CSF administration\n- Donor inclusion criteria: 2. Ability and willingness to provide written informed consent specific to this study\n- Donor inclusion criteria: 3. Male or female aged 18–65 years at time of consent\n- Donor inclusion criteria: 4. Body weight >40 kg and in good clinical condtition"}

Exclusion criteria

• {"criterion_text":"- 1.\taGvHD grade ≥II (per Appendix 1) or receiving systemic first-line therapy for any aGvHD. Skin GvHD grade II allowed\n- Patients with evidence of minimal residual disease during final assessment by consultant haematologist.\n- Uncontrolled infections unresponsive to treatment. Prophylactic therapy for CMV or EBV reactivation without disease evidence is allowed\n- HBV, HCV ή HIV positive patients\n- Receipt of any investigational agent ≤28 days before iG-Treg infusion. Agents outside study indication administered post-transplant (e.g., valganciclovir for CMV, MMF for GvHD prophylaxis) are allowed"}

Primary endpoints

• {"endpoint_text":"- To define the safety, tolerability, and maximum tolerable dose (MTD) of iG-Tregs for GvHD prophylaxis (Time frame: until 90 days following the infusion): - Incidence of infusion toxicity (within 1 hour of the infusion and graded according to CTCAE v. 4)","definition_or_measurement_approach":"Time frame: until 90 days following the infusion; incidence of infusion toxicity monitored within 1 hour of infusion and graded according to CTCAE v.4."}
• {"endpoint_text":"- Additional toxicities that may occur related to iG-Treg infusion (eg. Occurrence of exacerbation of GvHD, infections, disease relapse)","definition_or_measurement_approach":"Monitoring and recording of additional toxicities post-infusion including exacerbation of GvHD, infections, and disease relapse as safety events."}
• {"endpoint_text":"- Adverse effects occurring during the first 3 weeks following iG- Treg infusion will be accounted for the assessment of the safety profile and tolerability of each dose during the dose escalation phase (dose limiting toxicities, DLTs). One iG-Treg dose will be considered safe if DLT occurs only in 1/6 or 0/3 subjects of each cohort.","definition_or_measurement_approach":"DLTs defined as adverse effects in first 3 weeks post-infusion; dose considered safe if DLTs occur in ≤1/6 or 0/3 subjects per cohort (3+3 dose-escalation rules)."}

Secondary endpoints

• {"endpoint_text":"- Clinical efficacy of iG-Treg infusion in GvHD prophylaxis (Time frame: 52 weeks following allo-HCT): 1. Incidence and severity of GvHD","definition_or_measurement_approach":"Incidence and severity of GvHD assessed up to 52 weeks following allo-HCT."}
• {"endpoint_text":"- Day of cyclosporine (CsA) cessation","definition_or_measurement_approach":"Record the day of discontinuation of CsA prophylaxis."}
• {"endpoint_text":"- Treatment failure (includes the diagnosis GvHD, inability to cease CsA administration until d+150 following allo-HCT, disease relapse)","definition_or_measurement_approach":"Composite outcome including diagnosis of GvHD, failure to cease CsA by day +150 post allo-HCT, or disease relapse."}
• {"endpoint_text":"- Patients receiving iG-Tregs will be compared to a cohort not receiving the infusion of with retrospective data.","definition_or_measurement_approach":"Comparative analysis against a cohort without iG-Treg infusion or using retrospective/historical data."}

Greece

Earliest CTIS Part Ii Submission Date

05-12-2024

Latest Decision Or Authorization Date

26-02-2026

Processing Time Days

448

Number Of Sites

2

Number Of Participants

26

Primary sponsor

Full Name

University Of Patras

Organisation Type

Educational Institution

Country Of Registered Address

Greece

Contract research organisations

Name

Pharmassist Ltd.

Responsibilities

Sponsor third party with duties coded as 1,11,12,8 (contact: i.koukli@pharmassist-cro.com; phone +302106560700)

Third parties

• {"country":"Greece","full_name":"Pharmassist Ltd.","duties_or_roles":"duty codes: 1,11,12,8","organisation_type":"Pharmaceutical company"}