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

Prior treatment

• 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.
• 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.
• Known history of concomitant genetic syndromes such as Fanconi anemia, Schwachman-Diamond syndrome, Kostmann syndrome, or any other known BM failure syndrome.
• Patients who have received a prior stem cell transplant less than 3 months prior to CART84 infusion.
• If the patient participated in another experimental clinical trial within 1 month prior to CART84 infusion.

Other illness

• Isolated extramedullary (EM) disease.
• 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.
• Patients with active, life-threatening bleeding.
• Presence of uncontrolled fungal, bacterial, viral, or other infection requiring systemic antimicrobials for management.
• 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.
• 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).
• 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.

Lab values

• The following medications are excluded:
  • 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.
  • Immunosuppression: Immunosuppressive medication must be stopped ≥2 weeks prior to leukapheresis and CART84 infusion.
  • Allogeneic cellular therapy: Any donor lymphocyte infusions must be completed \>2 weeks prior to leukapheresis and not repeated thereafter.
  • 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.
  • Treatment with any T cell-lytic or toxic antibody (e.g. alemtuzumab) within 6 months prior to leukapheresis.
  • Intrathecal therapy within 2 weeks prior to starting pre-conditioning chemotherapy.

Other

• Females who are pregnant or lactating.
• For T-ALL patients: Patients with T-ALL exhibiting CD4+ and/or CD8+ immunophenotypes with detectable blasts in peripheral blood.
• Inability to tolerate leukapheresis.
• 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.

• Age 18 years or older at the time of signing the informed consent.
• Willing and able to give written, informed consent to the current study.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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:
  • Primary refractory disease (not achieving CR/CRi after more than two cycles of induction chemotherapy).
  • Second relapse or beyond.
  • Refractory relapse after at least 1 line of salvage therapy.
  • Relapsed or refractory disease after allogeneic transplant provided the CART84 infusion occurs at least 3 months after the stem cell transplant.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Adequate renal, hepatic, pulmonary, and cardiac function defined as:
  • Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 x ULN (upper limit of normal).
  • Creatinine clearance (as estimated by the Cockcroft Gault formula) ≥50 mL/min.
  • Total bilirubin ≤2 x ULN, except in patients with Gilbert's syndrome, who must have normal direct bilirubin.
  • Left ventricular ejection fraction (LVEF) ≥45% (or ≥institution's lower limit of normal) confirmed by ECHO or MUGA.
  • Baseline oxygen saturation \>92% on room air.