Safety and Efficacy of GYA01 (CART84) in Relapsed/Refractory (R/R) Acute Myeloid Leukemia (AML) and Acute Lymphoblastic T Leukemia Patients (T-ALL).

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).

This Phase I/IIa clinical study is testing an experimental treatment called GYA01 (CART84) for people with acute myeloid leukemia (AML) or T-cell acute lymphoblastic leukemia (T-ALL) whose disease has come back after treatment (relapsed) or did not respond to treatment (refractory).

GYA01 (CART84) is a type of CAR T-cell therapy. In this approach, a participant's own T cells (a type of immune cell) are collected and changed in a laboratory to help them better recognize and attack leukemia cells. The modified cells GYA01 (CART84) are then given back to the participant through an infusion into a vein.

The study is being done to:

Find a dose that can be given safely (Phase I) by treating small groups of participants with increasing dose levels and carefully monitoring side effects.

Look for early signs that GYA01 (CART84) may help control AML or T-ALL (Phase IIa).

Participants will be closely monitored for side effects and for changes in their leukemia after the infusion, and followed over time to understand safety and possible benefit.

Study Overview

• Status: Recruiting
• Conditions: Leukemia, T-Cell; Acute Myeloblastic Leukaemia
• Intervention / Treatment: Drug: CART84

Detailed Description

AML and T-ALL are aggressive cancers, with poor prognosis with currently available therapies and significant unmet medical needs. Despite advancements in conventional therapies, relapse and refractory disease remain major challenges, necessitating innovative therapeutic approaches.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of certain hematological malignancies and achieved excellent results in some cases and thus, there is robust rationale for expanding this therapeutic modality to R/R AML and T-ALL patients.

CD84 antigen is an immunoreceptor whose expression has been reported in certain immune cells and in B-cell malignancies. CD84 is overexpressed in AML and has been identified as a promising target for immunotherapy approaches, particularly CAR T-cell therapy. Although CD84 has been more extensively studied in the context of AML, it is a promising CAR T target for the treatment of several hematological malignancies.

Recently, CART84 cells were successfully expanded in vitro and exerted high cytotoxicity towards cell lines from different hematological malignancies, including AML and T-ALL. These findings suggest that CART84 cells may be a promising therapeutic option for patients with these diseases.

As such, this study is planned as a Phase I and Phase IIa trial, where the primary objective of Phase I is to evaluate the safety of CART84 cell therapy in patients with R/R AML and to determine the candidate dose for Phase II, where the clinical efficacy of CART84 at the recommended phase II dose (RP2D) level will be evaluated in AML and T-ALL patients.

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Claudio Santos, PhD; Phone Number: +34 684 765 219; Email: claudio.santos@gyalatx.com
• Study Contact Backup: Name: Teresa Galera, PhD, MBA; Email: teresa.galera@gyalatx.com

Study Locations

• Spain
  • Barcelona
    • Barcelona, Barcelona, Spain, 08036
      • Recruiting
      • Hospital Clinic De Barcelona
      • Contact: Jordi Esteve, MD; Phone Number: +34 932275428; Email: jesteve@clinic.cat
      • Contact: Interunit; Phone Number: 380427 +34932275400; Email: Intherun@recerca.clinic.cat
  • Valencia
    • Valencia, Valencia, Spain, 46026
      • Recruiting
      • Hospital Universitario y Politécnico La Fe
      • Contact: Pau Montesinos, MD; Phone Number: +34 961 245 876; Email: montesinos_pau@gva.es
      • Contact: Manuel Guerreiro, MD; Email: manuel_direito@iislafe.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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:

   1. Primary refractory disease (not achieving CR/CRi after more than two cycles of induction chemotherapy).
   2. Second relapse or beyond.
   3. Refractory relapse after at least 1 line of salvage therapy.
   4. Relapsed or refractory disease after allogeneic transplant provided the CART84 infusion occurs at least 3 months after the stem cell transplant.
5. Documentation of 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:

    1. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x ULN (upper limit of normal).
    2. Creatinine clearance (as estimated by the Cockcroft Gault formula) ≥50 mL/min.
    3. Total bilirubin ≤2 x ULN, except in patients with Gilbert's syndrome, who must have normal direct bilirubin.
    4. Left ventricular ejection fraction (LVEF) ≥45% (or ≥institution's lower limit of normal) confirmed by ECHO or MUGA.
    5. Baseline oxygen saturation >92% on room air.

Exclusion Criteria:

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:

    1. 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.
    2. Immunosuppression: Immunosuppressive medication must be stopped ≥2 weeks prior to leukapheresis and CART84 infusion.
    3. Allogeneic cellular therapy: Any donor lymphocyte infusions must be completed >2 weeks prior to leukapheresis and not repeated thereafter.
    4. 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.
    5. Treatment with any T cell-lytic or toxic antibody (e.g. alemtuzumab) within 6 months prior to leukapheresis.
    6. Intrathecal therapy within 2 weeks prior to starting pre-conditioning chemotherapy.
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 protocol-required study visits or procedures, including follow-up visits.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GYA01 (CART84)	Drug: CART84; GYA01 (CART84): autologous cell-based product containing CD3+ T cells transduced with a lentiviral vector expressing an anti-CD84 chimeric antigen receptor (CAR).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events.	Primary Outcome Measure Phase I and Secondary Outcome Measure Phase II: Frequency and severity of adverse events (AEs) and serious AEs (SAEs) occurring after CART84 infusion using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) grading for CRS/ICANS.	2 years
Proportion of patients achieving ORR after first infusion of CART84	Primary Outcome Measure Phase II and Secondary Outcome Measure Phase I: Proportion of patients achieving ORR at day 30 after first infusion of CART84 as assessed by European Leukemia Net (ELN) 2022 guidelines	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients achieving late ORR	Phases I & II: 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	day 90
Proportion of patients achieving measurable residual disease (MRD)-negative remission in bone marrow	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.	day 30
Proportion of CART84-infused patients undergoing allo-HSCT	Phases I & II: Proportion of CART84-infused patients undergoing allo-HSCT and achieving hematopoietic donor engraftment.	6 months
Proportion of patients with detectable CART84 cells	Phase I & II: 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.	Day 30 and Day 90
Proportion of enrolled patients for whom a CART84 product can be manufactured and administered as per protocol.	Phases I & II: Proportion of enrolled patients for whom a CART84 product can be manufactured and administered as per protocol.	3 months
Proportion of patients achieving MRD-negative remission	Phase II: 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).	24 months
Incidence of CD84-negative relapse.	Phase II: Incidence of CD84-negative relapse.	2 years
Hematologic recovery, based on serial peripheral blood counts after CART84 infusion.	Phase II: Hematologic recovery, based on serial peripheral blood counts after CART84 infusion.	90 days
Description of allo-HSCT procedures	Phase II: 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.	3 months

Collaborators and Investigators

• Sponsor: Gyala Therapeutics
• Collaborators: Astrum CRO, S.L.

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2026
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): February 4, 2031

Study Registration Dates

• First Submitted: March 10, 2026
• First Submitted That Met QC Criteria: March 10, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Cell Therapy; Gene Therapy; CAR-T; AML; T-ALL; CART; CART84; CD84; GYA01
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Myeloid; Leukemia, Lymphoid; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, T-Cell
• Other Study ID Numbers: GYA-CART84-AL-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: At the end of study SAP, OCF, CSR & Programming code will be shared
• IPD Sharing Time Frame: At the end of the study
• IPD Sharing Access Criteria: The documents will be uploaded to this website
• IPD Sharing Supporting Information Type: SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No