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.
• 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.