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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

CanCell Therapeutics

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2024-03-04

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Dose response, Pharmacogenomic, Pharmacodynamic, Pharmacokinetic, Efficacy

Phase 1 - To evaluate the safety, tolerability, and to define the recommended RP2D of CCTx-001
Phase 2 - To evaluate the clinical activity, as assessed by the composite complete response rate, in patients treated with CCTx-001

Secondary objectives 6

1. Phase 1 - To evaluate the clinical activity, as assessed by the composite complete response rate, in patients treated with CCTx-001
2. Phase 2 - To evaluate the clinical activity, as assessed by the complete remission rate, in patients treated with CCTx- 001
3. Phase 2 - To assess the safety of CCTx-001
4. Phase 2 - To assess HRQoL for patients treated with CCTx- 001
5. Phase 1 & 2 - To assess additional parameters of clinical activity in patients treated with CCTx-001
6. Phase 1 & 2 - To evaluate the overall safety and the tolerability of CCTx-001

Conditions and MedDRA coding

Relapsed/Refractory Acute Myeloid Leukemia (AML)

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut, Medicines Evaluation Board, National Agency For The Safety Of Medicine And Health Products

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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)
2. Have a circulating blast count of less than 20,000/mm3 (control with hydroxyurea is allowed)
3. Absolute Lymphocyte count of >200/mm3
4. Eastern Cooperative Oncology Group performance status ≤ 1
5. Life expectancy of more than 3 months
6. Age ≥ 18 years at the time of informed consent
7. Read, understood, and signed written informed consent form (ICF) prior to any study procedures
8. Eligible for leukapheresis
9. Adequate organ function
10. Women of childbearing potential must have a negative serum pregnancy test
11. 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

Exclusion criteria 18

1. Patients with acute promyelocytic leukaemia: t(15;17)(q22;q12); (promyelocytic leukaemia/retinoic acid receptor alpha) and variants
2. Patients with active central nervous system (CNS) leukaemia involvement or isolated extramedullary AML disease
3. Patients who underwent allo-HSCT within 90 days prior to leukapheresis
4. Patients with active GvHD
5. Patients who received previous treatment targeting IL-1RAP or previous gene therapy
6. 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
7. Patients with history or presence of an active and clinically relevant CNS disorder
8. Patients with active autoimmune disorders or active neurological or inflammatory disorders (e.g., Guillain-Barre Syndrome, Amyotrophic Lateral Sclerosis)
9. 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)
10. 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
11. Patients with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate anti-infection treatment
12. Active macrophage activation syndrome
13. Active or prior history of hepatitis B or hepatitis C infection
14. History of or active human immunodeficiency virus infection
15. Known hypersensitivity or contraindication to DMSO, cyclophosphamide, fludarabine, or their excipients
16. 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
17. 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
18. Pregnant or nursing women. NOTE: Women of reproductive potential must have a negative serum pregnancy test performed within 48 hours of starting LDC

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase 1 - Frequency, severity, relationship and persistence of AEs and DLTs
2. 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).

Secondary endpoints 6

1. 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).
2. 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.
3. Phase 2 - Frequency, severity, relationship and persistence of AEs
4. 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
5. 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
6. Phase 1 & 2 -Frequency and severity of AEs and laboratory abnormalities

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

CanCell Therapeutics

Sponsor organisation

CanCell Therapeutics

Address

8 Rue Docteur Jean Francois Xavier Girod

City

Besancon

Postcode

25000

Country

France

Scientific contact point

Organisation

CanCell Therapeutics

Contact name

CanCell Therapeutics

Public contact point

Organisation

CanCell Therapeutics

Contact name

CanCell Therapeutics

Locations

4 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications