Phase I/IIa clinical trial with dose escalation to evaluate safety and efficacy of the infusion of CART84 in relapsed/refractory (R/R) acute myeloid leukemia (AML) and acute lymphoblastic T leukemia patients (T-ALL).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gyala Therapeutics S.L.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Neoplasms [C04]

Trial duration

8 Sep 2025 → ongoing

Decision date (initial)

2025-08-12

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Gyala Therapeutics S.L.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Phase I:
To evaluate the safety and tolerability of CART84 and determine the candidate dose for phase 2.

Phase IIa:
To evaluate the clinical efficacy of CART84 at the RP2D measured as the overall response rate (ORR) defined as proportion of patients achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) or morphological leukemia-free state (MLFS).

Secondary objectives 10

1. Phase I: To evaluate the clinical efficacy of CART84.
2. Phase I: To evaluate the feasibility of successfully bridging patients to allogeneic hematopoietic stem cell transplantation (allo-HSCT) after infusion of CART84.
3. Phase I: To evaluate the expansion and persistence of CART84.
4. Phase I: To evaluate the feasibility of manufacturing and administering CART84.
5. Phase IIa: To evaluate the clinical efficacy of CART84.
6. Phase IIa: To assess the safety and tolerability of CART84.
7. Phase IIa: To evaluate the expansion and persistence of CART84.
8. Phase IIa: To evaluate incidence and duration of neutropenia and thrombocytopenia after CART84 infusion.
9. Phase IIa: To evaluate the feasibility of successfully bridging patients to allo-HSCT after infusion with CART84.
10. Phase IIa: To evaluate the feasibility of manufacturing and administering CART84.

Conditions and MedDRA coding

Relapsed/refractory Acute Lymphoblastic T Leukemia (T-ALL)

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age 18 years or older at the time of signing the informed consent.
2. Willing and able to give written, informed consent to the current study.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
4. Diagnosed with AML or T-ALL with ≥5% blasts in BM and/or PB at screening, without any approved therapeutic alternative and one of the following: a. Primary refractory disease (not achieving CR/CRi after more than two cycles of induction chemotherapy). b. Second relapse or beyond. c. Refractory relapse after at least 1 line of salvage therapy. d. Relapsed or refractory disease after allogeneic transplant provided the CART84 infusion occurs at least 3 months after the stem cell transplant.
5. Documentation of homogeneous CD84 expression on leukemic blasts in the BM and in peripheral blood, or other tissues if blasts are present, as assessed by flow cytometry at screening.
6. For T-ALL patients: diagnosed with T-ALL exhibiting a double-negative (CD4- CD8-) immunophenotype, or patients with CD4+ and/or CD8+ T-ALL with no detectable blasts in peripheral blood.
7. Availability of an appropriate HSCT donor, either related (haploidentical HLA matching or HLA identical sibling donor) or unrelated, if available within the required timeframe (days 30-90 post-CART84 infusion). If an unrelated donor is selected, it is highly recommended to have an haploidentical HLA matched donor identified and evaluated as a backup.
8. For females of childbearing potential (defined as <24 months after last menstruation or not surgically sterile), a negative serum or urine pregnancy test must be documented at screening, prior to pre-conditioning and confirmed before receiving the first dose of study treatment.
9. For females who are not postmenopausal (<24 months of amenorrhea) or who are not surgically sterile (absence of ovaries and/or uterus), commitment to the use of 2 methods of contraception, comprising of one highly effective method of contraception together with a barrier method, during the treatment period and for at least 12 months after the last dose of study treatment.
10. Male participants must agree to use 2 acceptable methods of contraception (one by the patient – usually a barrier method), and one highly effective method by the patient’s partner during the treatment period and for at least 12 months after the last dose of study treatment.
11. Adequate renal, hepatic, pulmonary, and cardiac function defined as: a. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x ULN (upper limit of normal). b. Creatinine clearance (as estimated by the Cockcroft Gault formula) ≥50 mL/min. c. Total bilirubin ≤2 x ULN, except in patients with Gilbert’s syndrome, who must have normal direct bilirubin. d. Left ventricular ejection fraction (LVEF) ≥45% (or ≥institution’s lower limit of normal) confirmed by ECHO or MUGA. e. Baseline oxygen saturation >92% on room air.

Exclusion criteria 17

1. Isolated extramedullary (EM) disease.
2. Females who are pregnant or lactating
3. For T-ALL patients: Patients with T-ALL exhibiting CD4+ and/or CD8+ immunophenotypes with detectable blasts in peripheral blood
4. History or presence of clinically relevant CNS pathology, such as epilepsy, paresis, aphasia, stroke within 3 months prior to enrollment, severe brain injuries, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis
5. Clinically significant, uncontrolled heart disease (New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, sick-sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities, unless the patient has a pacemaker) or a recent (within 12 months) cardiac event.
6. Patients with active, life-threatening bleeding
7. Presence of uncontrolled fungal, bacterial, viral, or other infection requiring systemic antimicrobials for management.
8. Positive serological testing for human immunodeficiency virus antibody, hepatitis B surface antigen, hepatitis B core antibody (anti-HBc), and hepatitis C virus antibody. Patients who are positive for anti-HBc or hepatitis C antibody may be included if they have a negative PCR test within 6 weeks prior to initial IMP administration
9. History of autoimmune disease (e.g., Crohn’s disease, rheumatoid arthritis, systemic lupus) resulting in organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 24 months, or any autoimmune disease with CNS involvement.
10. History of other malignant neoplasms unless disease-free for at least 12 months (carcinoma in situ, non-melanoma skin cancer, breast or prostate cancer on hormonal therapy allowed).
11. Known history of concomitant genetic syndromes such as Fanconi anemia, Schwachman-Diamond syndrome, Kostmann syndrome, or any other known BM failure syndrome.
12. Patients who have received a prior stem cell transplant less than 3 months prior to CART84 infusion.
13. Active significant (overall Grade ≥II, Seattle criteria) acute graft-versus-host disease (GvHD) or moderate/severe chronic GvHD (NIH consensus criteria) requiring systemic steroids or other immunosuppressants within 4 weeks of consent.
14. The following medications are excluded: a. Steroids: Therapeutic doses of corticosteroids (greater than 10 mg daily of prednisone or its equivalent) within 7 days of leukapheresis or 72 hours prior to CART84 administration. However, physiological replacement, topical, and inhaled steroids are permitted. b. Immunosuppression: Immunosuppressive medication must be stopped ≥2 weeks prior to leukapheresis and CART84 infusion. c. Allogeneic cellular therapy: Any donor lymphocyte infusions must be completed >2 weeks prior to leukapheresis and not repeated thereafter. d. Graft-versus-host disease therapies: Any drug used for the treatment of GvHD must be stopped >2 weeks prior to leukapheresis and not repeated thereafter. e. Treatment with any T cell-lytic or toxic antibody (e.g. alemtuzumab) within 6 months prior to leukapheresis. f. Intrathecal therapy within 2 week
15. If the patient participated in another experimental clinical trial within 1 month prior to CART84 infusion
16. Inability to tolerate leukapheresis.
17. Patients who, in the opinion of the Investigator, may not be able to understand or comply with the safety monitoring requirements of the study or unlikely to complete all protocolrequired study visits or procedures, including follow-up visits.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase I: Frequency and severity of AEs and SAEs occurring after CART84 infusion using the CTCAE V 5.0 and ASTCT grading for CRS/ICANS. The following AEs will be considered AESI: Infusion reactions, tumor lysis syndrome (TLS), CRS, ICANS,, immune effector cell associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), prolonged cytopenia grade >3 (beyond 6 months), hepatitis B reactivation, infections meeting SAE criteria, and second neoplasms.
2. Phase IIa: Proportion of patients achieving ORR at day 30 after first infusion of CART84 as assessed by European Leukemia Net (ELN) 2022 guidelines.

Secondary endpoints 15

1. Phase I: Proportion of patients achieving ORR at day 30 after first infusion of CART84 as assessed by European Leukemia Net (ELN) 2022 guidelines
2. Phase I: Proportion of patients achieving late ORR, defined as a response occurring after day 30 and up to day 90, provided that no other therapy has been administered (additional CART84 cell infusions beyond day 30 are allowed in specific situations, as per protocol).
3. Phase I: Proportion of patients achieving measurable residual disease (MRD)-negative remission in bone marrow (BM) by polymerase chain reaction (PCR) and/or flow cytometry at day 30
4. Phase I: Proportion of CART84-infused patients undergoing allo-HSCT (and achieving hematopoietic donor engraftment).
5. Phase I: Proportion of patients with detectable CART84 cells by PCR in peripheral blood and/or bone marrow (BM) at day 30 and day 90 following CART84 infusion, comparing those who proceed to allo-HSCT versus those who do not at the last follow-up.
6. Phase I: Proportion of enrolled patients for whom a CART84 product can be manufactured and administered as per protocol.
7. Phase IIa: Proportion of patients achieving late ORR, defined as occurring after day 30 and until day 90, given that no additional therapy outside the protocol has been received
8. Phase IIa: Proportion of patients achieving MRD-negative remission, CR, duration of response (DoR) according to allo-HSCT (at day 30, 6, 12 and 24 months following CART84 infusion), relapse-free survival (RFS), event-free survival (EFS), overall survival (OS).
9. Phase IIa: Incidence of CD84-negative relapse.
10. Phase IIa: Frequency and severity of AEs and SAEs. The following AEs will be considered of special interest (AESI): Infusion reactions, tumor lysis syndrome (TLS), CRS, ICANS,, immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS), prolonged cytopenia grade >3 (beyond 6 months), hepatitis B reactivation, infections meeting SAE criteria, and second neoplasms
11. Phase IIa: Detection of CART cells measured by PCR in the peripheral blood and BM following CART84 infusion.
12. Phase IIa: Hematologic recovery, based on serial peripheral blood counts after CART84 infusion.
13. Phase IIa: Percentage of CART84-infused patients undergoing allo-HSCT (and achieving hematopoietic donor engraftment).
14. Phase IIa: Description of allo-HSCT procedures (donor type, conditioning, stem-cell source, GvHD prophylaxis) and related complications: graft failure, incidence and grading of acute and chronic GvHD, infection, other organ-related toxicities such as SOS, cardiotoxicity, or non-relapse mortality (NRM) with all associated causes.
15. Phase IIa: Proportion of enrolled patients for whom a CART84 product can be manufactured and administered as per protocol.

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gyala Therapeutics S.L.

Sponsor organisation

Gyala Therapeutics S.L.

Address

Paseo De Gracia 54 2d

City

Barcelona

Postcode

08007

Country

Spain

Scientific contact point

Organisation

Gyala Therapeutics S.L.

Contact name

Medical & Scientific Department

Public contact point

Organisation

Gyala Therapeutics S.L.

Contact name

Medical & Scientific Department

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