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

NCT06281847 | Not Yet Recruiting Phase 1

• 1 other identifier: CCTx-001-AML-001
• Study Type: interventional
• Target: 143
• Locations: 4 countries
• Sites: 6

Brief Summary

The purpose of this adaptive Phase 1/2 study is to evaluate the safety, tolerability, pharmacokinetics (PK), and antileukemic activity of CCTx-001 in adult patients with r/r Acute Myeloid Leukemia (AML). CCTx-001 targets IL-1RAP, which is specifically expressed in leukemic cells. In preclinical studies, IL-1RAP-targeted Chimeric antigen receptors (CARs) have demonstrated encouraging activity in both in vitro and in vivo experiments in AML models. Based on these promising preclinical results, it is expected that CCTx-001 could potentially alter the natural course of r/r AML and provide a potential novel treatment option.

Conditions

Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory

Keywords

Acute Myeloid Leukemia; Relapsed; Refractory; Open-label; Safety; Tolerability

Outcome Measures

Primary Outcomes (2)

• Phase 1: To evaluate the safety, tolerability, and to define the recommended phase 2 dose (RP2D) of CCTx-001

  Frequency, severity, relationship and persistence of adverse events (AEs) and dose-limiting toxicity (DLTs)

  Up to 28 days

• Phase 2: To evaluate the clinical activity, as assessed by the composite complete response rate, in patients treated with CCTx-001

  Composite complete response rate (cCRR) defined as the proportion of patients with best overall response, as assessed by Independent Review Committee (IRC) based on European LeukemiaNet (ELN) 2022 criteria, at complete remission (CR), CR with partial haematologic recovery (CRh), or CR with incomplete haematologic recovery (CRi).

  Up to 3 months

Secondary Outcomes (13)

• Phase 2: To evaluate the clinical activity, as assessed by the complete remission rate, in patients treated with CCTx-001

  Up to 3 months

• Phase 1: To evaluate the clinical activity, as assessed by the composite complete response rate, in patients treated with CCTx-001

  Up to 3 months

• Phase 2: To assess the safety of CCTx-001

  Up to 15 years

• Phase 1 & 2: To assess additional parameters of clinical activity in patients treated with CCTx-001

  Up to 3 months

• Phase 1 & 2: To assess additional parameters of clinical activity in patients treated with CCTx-001

  Up to 24 months

Study Arms (1)

Open Label CCTx-001 infusion

EXPERIMENTAL

CCTx-001 infusion 2 to 7 days after completion of LDC

Genetic: CCTx-001

Interventions

CCTx-001 GENETIC

Frozen CAR T-cells suspensions in media containing dimethyl sulfoxide (DMSO)

Open Label CCTx-001 infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with active (\> 5 % blasts in bone marrow) r/r AML (WHO 2022) who have exhausted their therapeutic alternatives or have contraindications to these alternatives as judged by the treating physician defined as either:
• a. Primary refractory: i. 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 ii. Older patients or patients unfit to receive intensive induction courses who failed after two cycles of venetoclax + azacitidine or 4 cycles of azacitidine b. Relapsing: i. Patients with early relapse after CR to first line therapy (within ≤ 6 months after CR1) or ii. Patients with relapse after later lines of therapy (Relapse after CR≥2) c. Patients relapsing after allogeneic hematopoietic stem cell transplant: i. Patients must be at least 3 months from hematopoietic stem cell transplant (HSCT) at the time of consent, and ii. Off immunosuppression for at least 1 month at the time of consent, and iii. Have no active graft versus host disease (GvHD)
• 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 (ECOG) performance status ≤ 1
• Life expectancy of more than 3 months
• Patient is ≥ 18 years of age at the time of informed consent
• Read, understood, and signed the informed consent form (ICF) prior to any study procedures
• Patient is willing and able to adhere to the study visit schedule and other protocol requirements
• Eligible for leukapheresis
• Treatment-related toxicities of previous therapies have completely resolved
• Adequate organ function as confirmed by clinical laboratory values, defined as:
• Adequate bone marrow function to receive LDC as assessed by the Investigator
• Serum creatinine \[\< 1.5 x the upper limit of normal (ULN) or creatinine clearance (CrCl) \> 45 mL/min\] (estimated by Cockcroft Gault or Modification of Diet in Renal Disease (MDRD); see Appendix 14.3 for calculation)
• Alanine aminotransferase \[≤ 3 x ULN and total bilirubin \< 1.5 mg/dL (or \< 3.0 mg/dL\] for patients with Gilbert's syndrome or leukemic infiltration of the liver)\]

You may not qualify if:

• Patients with an acute promyelocytic leukaemia: t(15;17)(q22;q12); (promyelocytic leukaemia/retinoic acid receptor alpha) and variants
• Patients with active central nervous system (CNS) leukaemia involvement. If the patient has prior history of CNS leukaemia, they must have a negative cerebrospinal fluid (CSF) assessment and magnetic resonance imaging (MRI) or computed tomography (if MRI is not feasible) of the brain demonstrating no evidence of CNS disease
• Patients with isolated extramedullary AML disease
• Patients who received previous treatment targeting IL-1RAP or previous gene therapy
• Patients who underwent allo-HSCT within 90 days prior to leukapheresis
• Patients who received donor lymphocyte infusion within 60 days prior to leukapheresis
• Patients with active GvHD
• 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
• Other completely resected stage 1 solid tumour with low risk for recurrence
• Presence of systemic fungal, bacterial, viral, or other infection (including tuberculosis) that is uncontrolled despite appropriate antibiotics or other treatments

Sponsors & Collaborators

• Advesya SAS: lead

Study Sites (6)

Besançon Regional and University Hospital

Besançon, France

Location

Hospital Saint Louis

Paris, France

Location

Ludwig-Maximilians University of Munich

Munich, Germany

Location

University Hospital Ulm

Ulm, Germany

Location

Vall d'Hebron University Hospital

Barcelona, Spain

Location

Karolinska University Hospital

Stockholm, Sweden

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study comprises 4 periods: * The pre-treatment period will consist of screening for eligibility, leukapheresis and a pre-treatment evaluation (prior to Lymphodepleting Chemotherapy (LDC)). * The treatment period will start with LDC, followed by CCTx-001 infusion 2 to 7 days after completion of LDC. A first response evaluation will be performed at approximately 28 days after CCTx-001 infusion. * The post-treatment period will consist of further clinical activity and safety follow-up visits at regular timepoints after CCTx-001 infusion, starting after the Month 3 visit up to the Month 24 visit. * The long-term follow-up period will start after the Month 24 visit up to 15 years post CCTx-001 infusion.

Study Record Dates

• First Submitted: February 6, 2024
• First Posted: February 28, 2024
• Study Start: December 1, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): August 1, 2041
• Last Updated: September 18, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); SE (1); ES (1); FR (2)