CCTX-001 for Acute myeloid leukemia (relapsed/refractory)

Inclusion criteria

• {"criterion_text":"- 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)\n- Women of childbearing potential must have a negative serum pregnancy test\n- 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\n- Have a circulating blast count of less than 20,000/mm3 (control with hydroxyurea is allowed)\n- Absolute Lymphocyte count of >200/mm3\n- Eastern Cooperative Oncology Group performance status ≤ 1\n- Life expectancy of more than 3 months\n- Age ≥ 18 years at the time of informed consent\n- Read, understood, and signed written informed consent form (ICF) prior to any study procedures\n- Eligible for leukapheresis\n- Adequate organ function"}

Exclusion criteria

• {"criterion_text":"- Patients with acute promyelocytic leukaemia: t(15;17)(q22;q12); (promyelocytic leukaemia/retinoic acid receptor alpha) and variants\n- 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\n- Patients with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate anti-infection treatment\n- Active macrophage activation syndrome\n- Active or prior history of hepatitis B or hepatitis C infection\n- History of or active human immunodeficiency virus infection\n- Known hypersensitivity or contraindication to DMSO, cyclophosphamide, fludarabine, or their excipients\n- 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\n- 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\n- Pregnant or nursing women. NOTE: Women of reproductive potential must have a negative serum pregnancy test performed within 48 hours of starting LDC\n- Patients with active central nervous system (CNS) leukaemia involvement or isolated extramedullary AML disease\n- Patients who underwent allo-HSCT within 90 days prior to leukapheresis\n- Patients with active GvHD\n- Patients who received previous treatment targeting IL-1RAP or previous gene therapy\n- 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\n- Patients with history or presence of an active and clinically relevant CNS disorder\n- Patients with active autoimmune disorders or active neurological or inflammatory disorders (e.g., Guillain-Barre Syndrome, Amyotrophic Lateral Sclerosis)\n- 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)"}

Primary endpoints

• {"endpoint_text":"- Phase 1 - Frequency, severity, relationship and persistence of AEs and DLTs","definition_or_measurement_approach":"Safety endpoints assessed by recording frequency, severity, relationship and persistence of adverse events (AEs) and dose-limiting toxicities (DLTs) as reported during Phase 1."}
• {"endpoint_text":"- Phase 2 - Composite complete response rate (cCRR) defined as the proportion of patients with best overall response, as assessed by IRC based on ELN 2022 criteria, at complete remission (CR), CR with partial haematologic recovery (CRh), or CR with incomplete haematologic recovery (CRi).","definition_or_measurement_approach":"cCRR defined as proportion of patients with best overall response assessed by Independent Review Committee (IRC) using ELN 2022 criteria at CR, CRh, or CRi."}

Secondary endpoints

• {"endpoint_text":"- Phase 1 - Composite complete response rate (cCRR) defined as the proportion of patients with best overall response, as assessed by IRC based on ELN 2022 criteria, at complete remission (CR), CR with partial haematologic recovery (CRh), or CR with incomplete haematologic recovery (CRi).","definition_or_measurement_approach":"cCRR defined as proportion with best overall response assessed by IRC per ELN 2022 criteria (CR, CRh, CRi)."}
• {"endpoint_text":"- Phase 2 - Complete remission rate (CRR) defined as the proportion of patients with best overall response, as assessed by IRC based on ELN 2022 criteria, at CR.","definition_or_measurement_approach":"CRR defined as proportion with best overall response of CR assessed by IRC per ELN 2022 criteria."}
• {"endpoint_text":"- Phase 2 - Frequency, severity, relationship and persistence of AEs","definition_or_measurement_approach":"Safety assessed by recording frequency, severity, relationship and persistence of adverse events."}
• {"endpoint_text":"- Phase 2 - Changes in HRQoL using global health/QoL, fatigue, physical and cognitive functioning subscales of the EORTC QLQ-C30, and the HM-PRO tools","definition_or_measurement_approach":"Health-related quality of life measured by EORTC QLQ-C30 subscales and HM-PRO instruments."}
• {"endpoint_text":"- Phase 1 & 2 - Objective response rate (ORR), event-free survival (EFS), relapse-free survival (RFS), overall survival (OS), duration of response (DOR), cumulative incidence of relapse (CIR), cumulative incidence of death (CID), time to composite complete response (TTcCR), and time to response (TTR) according to ELN 2022 criteria, and MRD responses","definition_or_measurement_approach":"Efficacy endpoints assessed per ELN 2022 criteria including ORR, EFS, RFS, OS, DOR, CIR, CID, TTcCR, TTR, and measurable residual disease (MRD) responses as defined in protocol."}
• {"endpoint_text":"- Phase 1 & 2 -Frequency and severity of AEs and laboratory abnormalities","definition_or_measurement_approach":"Safety and tolerability assessed by recording frequency and severity of adverse events and laboratory abnormality reporting."}

Spain

Earliest CTIS Part Ii Submission Date

16-10-2023

Latest Decision Or Authorization Date

17-07-2024

Processing Time Days

275

Number Of Sites

1

Number Of Participants

8

Germany

Earliest CTIS Part Ii Submission Date

16-10-2023

Latest Decision Or Authorization Date

24-06-2024

Processing Time Days

252

Number Of Sites

2

Number Of Participants

23

France

Earliest CTIS Part Ii Submission Date

20-11-2023

Latest Decision Or Authorization Date

24-06-2024

Processing Time Days

217

Number Of Sites

2

Number Of Participants

23

Sweden

Earliest CTIS Part Ii Submission Date

29-09-2023

Latest Decision Or Authorization Date

20-06-2024

Processing Time Days

265

Number Of Sites

1

Number Of Participants

7

Primary sponsor

Full Name

CanCell Therapeutics

Organisation Type

Pharmaceutical company

Country Of Registered Address

France