Phase I/II Study of inducible HLAG+ Regulatory T Cells (iG-Tregs) in patients undergoing HLA-matched sibling donor allogeneic haematopoietic cell transplantation.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Patras

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

26 May 2023 → ongoing

Decision date (initial)

2025-01-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-520084-14-00

EudraCT number

2021-006367-26

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Dose response

-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 objectives 1

1. To determine the clinical efficacy of iG-Tregs cells in the prevention of aGvHD by allowing the rapid cessation of prophylactic immunosuppression.

Conditions and MedDRA coding

Adopt immunotherapy in adult patients undergoing hematopoietic stem cell (HSCT) transplantation from a fully compatible donor sibling for the prevention and treatment of GvHD.

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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.
2. 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 Absolute neutrophil count (ANC) >1 x 10^9/L o Serum creatinine ≤2 mg/dL or GFR >40 mL/min/1.73 m² o AST or ALT <3 x upper limit of normal (ULN) o Total bilirubin ≤2.5 mg/dL (not applied to participants with Gilbert’s syndrome) o Albumin >2.5 g/dL o Oxygen saturation ≥92% on room air o Chest X-ray or CT scan without signs of infection o No significant cardiac disease and/or left ventricular ejection fraction >35% on echocardiogram
3. 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
4. Patient inclusion criteria: 4. Ability to understand and willingness to sign the approved informed consent form after explanation
5. 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
6. 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
7. Donor inclusion criteria: 2. Ability and willingness to provide written informed consent specific to this study
8. Donor inclusion criteria: 3. Male or female aged 18–65 years at time of consent
9. Donor inclusion criteria: 4. Body weight >40 kg and in good clinical condtition
10. Donor inclusion criteria: 5. HLA-matched sibling donor of the patient’s hematopoietic stem cells
11. 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)

Exclusion criteria 5

1. 1. aGvHD grade ≥II (per Appendix 1) or receiving systemic first-line therapy for any aGvHD. Skin GvHD grade II allowed
2. Patients with evidence of minimal residual disease during final assessment by consultant haematologist.
3. Uncontrolled infections unresponsive to treatment. Prophylactic therapy for CMV or EBV reactivation without disease evidence is allowed
4. HBV, HCV ή HIV positive patients
5. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. 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)
2. Additional toxicities that may occur related to iG-Treg infusion (eg. Occurrence of exacerbation of GvHD, infections, disease relapse)
3. 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.

Secondary endpoints 4

1. Clinical efficacy of iG-Treg infusion in GvHD prophylaxis (Time frame: 52 weeks following allo-HCT): 1. Incidence and severity of GvHD
2. Day of cyclosporine (CsA) cessation
3. Treatment failure (includes the diagnosis GvHD, inability to cease CsA administration until d+150 following allo-HCT, disease relapse)
4. Patients receiving iG-Tregs will be compared to a cohort not receiving the infusion of with retrospective data.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Patras

Sponsor organisation

University Of Patras

Address

University Campus

City

Patra

Postcode

265 04

Country

Greece

Scientific contact point

Organisation

University Of Patras

Contact name

Alexandros Spyridonidis

Public contact point

Organisation

University Of Patras

Contact name

Alexandros Spyridonidis

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications