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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
GYA01 (CART84): autologous cell-based product containing CD3+ T cells transduced with a lentiviral vector expressing an anti-CD84 chimeric antigen receptor (CAR).
Hospital Clínic de Barcelona
Barcelona, Barcelona, Spain
RECRUITINGHospital Universitario y Politécnico La Fe
Valencia, Valencia, Spain
RECRUITINGNumber 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.
Time frame: 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
Time frame: 30 days
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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 24 months
Incidence of CD84-negative relapse.
Phase II: Incidence of CD84-negative relapse.
Time frame: 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.
Time frame: 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.
Time frame: 3 months
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