An adaptive open-label multicentre phase 1/2 trial, to determine the recommended phase 2 dose of CCTx-001, and to assess safety, tolerability, and clinical activity in patients with relapsed/refractory acute myeloid leukaemia (RESOLVE AML 001)

Prior treatment

• Use of therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis, and within 72 hours prior to CCTx-001 infusion. Physiologic replacement, topical, and inhaled steroids are permitted
• Active or prior history of hepatitis B or hepatitis C infection
• History of any of the following cardiovascular conditions within the past 6 months prior to signing the ICF: Class III or IV heart failure as defined by the New York Heart Association, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease
• Patients who underwent allo-HSCT within 90 days prior to leukapheresis
• Patients who received previous treatment targeting IL-1RAP or previous gene therapy
• Use of immunosuppressive therapies within 4 weeks prior to signing the ICF (e.g., calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-tumour necrosis factor, anti-interleukin 6, or anti-interleukin 6 receptor)

Other illness

• Patients with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate anti-infection treatment
• Active macrophage activation syndrome
• History of or active human immunodeficiency virus infection
• Known hypersensitivity or contraindication to DMSO, cyclophosphamide, fludarabine, or their excipients
• Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as judged by the Investigator; or unwillingness or inability to follow the procedures required in the protocol
• Patients with active central nervous system (CNS) leukaemia involvement or isolated extramedullary AML disease
• Patients with history or presence of an active and clinically relevant CNS disorder
• Patients with active autoimmune disorders or active neurological or inflammatory disorders (e.g., Guillain-Barre Syndrome, Amyotrophic Lateral Sclerosis)

Lab values

• Pregnant or nursing women. NOTE: Women of reproductive potential must have a negative serum pregnancy test performed within 48 hours of starting LDC

Age

• Patients with history of another primary malignancy other than disease under study unless the patient has been free of the disease for ≥ 2 years, except for the following non-invasive malignancies: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histologic finding of prostate cancer (T1a or T1b) or prostate cancer that is curative, or other completely resected stage 1 solid tumour with low risk of recurrence

Other

• Patients with acute promyelocytic leukaemia: t(15;17)(q22;q12); (promyelocytic leukaemia/retinoic acid receptor alpha) and variants
• Patients with active GvHD

• Patients with active (> 5 % blasts in bone marrow) r/r AML defined as either: 1. Primary refractory: a. Patients who failed after two cycles of intensive induction including high-dose and/or standard dose cytarabine (including liposomal formulation), +/- anthracycline, +/- antimetabolite, +/- targeted therapy OR b. Older patients or patients unfit to receive intensive induction courses who failed after two cycles of venetoclax + azacitidine or 4 cycles of azacitidine 2. Relapsing: a. Patients with early relapse after CR to first line therapy (within ≤ 6 months after CR1) OR b. Patients with relapse after later lines of therapy (Relapse after CR≥2) 3. Patients relapsing after allogeneic hematopoietic stem cell transplant: a. Patients must be at least 3 months from HSCT at the time of consent, AND b. Off immunosuppression for at least 1 month at the time of consent, AND c. Have no active graft versus host disease (GvHD)
• Women of childbearing potential must have a negative serum pregnancy test
• Patients in reproductive age must be able and willing to use at least 1 highly effective method of contraception during the study and for 12 months after the last dose of LDC
• Have a circulating blast count of less than 20,000/mm3 (control with hydroxyurea is allowed)
• Absolute Lymphocyte count of >200/mm3
• Eastern Cooperative Oncology Group performance status ≤ 1
• Life expectancy of more than 3 months
• Age ≥ 18 years at the time of informed consent
• Read, understood, and signed written informed consent form (ICF) prior to any study procedures
• Eligible for leukapheresis
• Adequate organ function