CARLA-M19 : “Prospective non-randomized phase I/II study investigating the safety of CD19 CAR-T cells in patients with refractory/relapsed AML (Acute Myeloïd Leukemia) expressing CD19.”

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Lille

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

10 Jul 2025 → ongoing

Decision date (initial)

2024-10-07

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BPI-CHU Lille 2019

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To investigate the safety and tolerability of the administration of academically produced CD19 CAR-T cells.

Secondary objectives 3

1. Feasibility of the process of production
2. Persistence of CAR-T cells over time in the patients
3. Efficacy at one year after the infusion of CAR-T cells in terms of disease control.

Conditions and MedDRA coding

Patients (male or female) ≥18 years old with R/R AML that expresses CD19 by Flow-cytometry

Regulatory references

Plan to share IPD

No

IPD plan description

Data will be enterred in eCRF which will accessible only to the authorized person.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
2. Patient with AML that expresses CD19 by Flow-cytometry
3. Patients with R/R AML defined as: • Primary refractory: absence of remission after two courses of induction chemotherapy, • Secondary refractory: absence of remission after salvage treatment in relapsing patients, • Post-transplant relapse in patients having had allo-HCT
4. Eastern Cooperative Oncology Group (ECOG) performance status of < 2
5. Estimated life expectancy of > 2 months
6. Magnetic resonance imaging (MRI) of the brain showing no evidence of central nervous system (CNS) involvement
7. Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities, such as alopecia).
8. Platelet count ≥ 30000/uL.
9. Absolute lymphocyte count ≥ 200/uL
10. Creatinine clearance (as estimated by Cockcroft Gault) ≥ 40 mL/min
11. Serum ALT/AST ≤ 2.5 upper limit of normal (ULN).
12. Total bilirubin ≤ 1.5 mg/dL, except in subjects with Gilbert’s syndrome
13. Cardiac ejection fraction ≥ 45 %.
14. No clinically significant electrocardiogram (ECG) findings
15. No clinically significant pleural effusion
16. Baseline oxygen saturation > 92 % on room air
17. Female patients of childbearing potential must: a. have a negative pregnancy test (blood) at screening visit. b. either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, effective measures of contraception without interruption, from screening through 1 year following the CAR-T cell infusion. A highly effective method of contraception or birth control (failure rate less than 1% per year when used consistently and correctly) must be practiced. The patient should be informed of the potential risks associated with becoming pregnant while enrolled in this clinical trial. Reliable methods for this trial are: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, sexual abstinence or vasectomized sexual partner. Abstinence is only accepted as true abstinence: when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence [e.g. calendar, ovulation, symptothermal, post-ovulation methods and withdrawal] are not acceptable methods of contraception.) Postmenopausal (no menses for at least 1 year without alternative medical cause) or surgically sterile female patients (tubal ligation, hysterectomy or bilateral oophorectomy) may be enrolled. c. Agree to abstain from breast feeding during the study participation and for 1 year after the CAR-T cell infusion. Male patients must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential for at least 1 year after the CAR-T cell infusion, even if he has undergone a successful vasectomy.

Exclusion criteria 14

1. Patient unable to sign the informed consent
2. Patient with R/R AML that does not expresses CD19
3. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease-free and without anticancer therapy for at least 3 years
4. Prior CD19 targeted therapy
5. Prior CAR therapy or other genetically modified T cell therapy
6. Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management
7. History of human immunodeficiency virus (HIV) or HTLV1
8. Infection or acute or chronic active hepatitis C infection
9. Infection or acute or chronic active hepatitis (Hep) B. Subjects with history of Hep B or Hep C infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines
10. Subjects with detectable cerebrospinal fluid malignant cells or known brain metastases or with a history of cerebrospinal fluid (CSF) malignant cells or brain metastases
11. History or presence of non-malignant CNS disorder, such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
12. Patient placed under guardianship or curatoship
13. Females either pregnant/breast-feeding or planning to become pregnant
14. Absence of medical insurance cover

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Number of patients deceased without progression at one month after CAR T-cell infusion. Non-progression mortality (NPM). NPM is defined as death occurred in patients without evidence of AML progression. Absence of response, progression or relapse of AML define progression status

Secondary endpoints 7

1. Number of patients with manufacturing failure and out of specification (OOS) deviation
2. Duration of CAR-T cell persistence in blood after infusion evaluated by flow-cytometry and PCR
3. Number of patients with overall response at one-month
4. Response duration, and number of patients alive at 3, 6 and 12 months
5. Number of patients alive without relapse at 3, 6 and 12 months
6. Number of deaths without progression at 3, 6 and 12 months
7. Number of patients with complete remission (CR) at 1 and 3 months

Investigational products

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

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Lille

Sponsor organisation

Centre Hospitalier Universitaire De Lille

Address

2 Avenue Oscar Lambret, Cs 70001 Cs 70001

City

Lille Cedex

Postcode

59037

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Lille

Contact name

Professor Ibrahim YAKOUB-AGHA

Public contact point

Organisation

Centre Hospitalier Universitaire De Lille

Contact name

Professor Ibrahim YAKOUB-AGHA

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Documents 7 files

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

Application history

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