Relapsed Adult AMLPhase 1CARLA-M19NCT06649227
Study Investigating the Safety of CD19 CAR-T Cells in Relapsed/Refractory AML Expressing CD19
A Phase 1 study testing CAR-T cell therapy in people with Relapsed Adult AML, run by University Hospital, Lille at 1 site in France.
Trial summary
Refractory/Relapsed (R/R) acute myeloid leukemia (AML) is associated with a dis-mal prognosis. In some subsets of AML such as AML driven by the t(8;21) translocation, leading to the RUNX1-RUNX1T1 (AML1-ETO) fusion transcript expression, CD19 B-cell antigen is aberrantly expressed on malignant blasts in around 80 % of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed Adult AML
- What is being tested?
- CAR-T cell therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteFrance
- Study dates
- 10 Jul 2025to 10 Jul 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is ≥ 18 years of age at the time of signing the informed consent form,
- Patient with AML that expresses CD19 by Flow-cytometry, (CD19 expression ≥ 70% of AML blasts)
- 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.
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- Lack of accessible targeted therapy that has not been previously utilized.
- Eastern Cooperative Oncology Group (ECOG) performance status of < 2,
- Estimated life expectancy of > 2 months,
- Magnetic resonance imaging (MRI) of the brain showing no evidence of central nervous system (CNS) involvement,
- Toxicities due to prior therapy must be stable and recovered to ≤ Grade 1 (except for clinically non-significant toxicities, such as alopecia),
- Platelet count ≥ 30000/uL,
- Absolute lymphocyte count ≥ 200/uL,
- Creatinine clearance (as estimated by Cockcroft Gault) ≥ 40 mL/min,
- Serum ALT/AST ≤ 2.5 upper limit of normal (ULN),
- Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome,
- Cardiac ejection fraction ≥ 45 %,
- No clinically significant electrocardiogram (ECG) findings,
- No clinically significant pleural effusion,
- Baseline oxygen saturation > 92 % on room air,
- Female patients of childbearing potential must:
- have a negative pregnancy test (blood) at screening visit.
- 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.
- 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.
Who cannot join
- Patient unable to sign the informed consent,
- Patient with R/R AML that does not expresses CD19,
- 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,
- Prior CD19 targeted therapy,
- Prior CAR therapy or other genetically modified T cell therapy,
- Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management,
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- History of human immunodeficiency virus (HIV) or HTLV1,
- Infection or acute or chronic active hepatitis C infection,
- 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,
- Subjects with detectable cerebrospinal fluid malignant cells or known brain metastases or with a history of cerebrospinal fluid (CSF) malignant cells or brain metastases,
- 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,
- Patient placed under guardianship or curatorship,
- Females either pregnant/breast-feeding or planning to become pregnant,
- Any contraindication due to hypersensitivity to the active substance or to any of the excipients,
- Contraindication to the lymphodepleting chemotherapy,
- Absence of medical insurance cover.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
CHU de Lille
Lille, 59000
Ibrahim Yakoub-Agha, Prof
About this study
Official title: Prospective Non-randomized Phase I Study Investigating the Safety of CD19 CAR-T Cells in Patients With Refractory/Relapsed AML Expressing CD19.
Refractory/Relapsed (R/R) acute myeloid leukemia (AML) is associated with a dis-mal prognosis.
In some subsets of AML such as AML driven by the t(8;21) translocation, leading to the RUNX1-RUNX1T1 (AML1-ETO) fusion transcript expression, CD19 B-cell antigen is aberrantly expressed on malignant blasts in around 80 % of cases. Interestingly, the expression of the CD19 antigen is also detected in the CD34+ CD38-population leukemic stem cells.
Read more
t(8;21) AML subtype has a rather good prognosis with an intensive chemotherapy regimen, but relapses occur in around 40 % of the patients and new therapeutic options are needed for these patients.
Plesa et al, reported a successful treatment of a refractory t(8;21) AML with bispecific monoclonal antibodies that targets CD19. More recently, Danylesko et al, have reported long-term remission following CD19 CAR-T cells in a heavily pre-treated patient with t(8;21) AML(1). The same group has just submitted an abstract of 6 treated patients to the European Haematology Association (EHA) 2023 meet-ing: Six patients (adults-5, child-1) with t(8; 21) AML (confirmed by cytogenetic and FISH) and aberrant CD19 expression were included. One patient had a complex karyotype. Molecular analysis for CKIT, NPM1, IDH1, IDH2, and CBPa were nega-tive in all pts. One pt harbors the FLT3 ITD and TKD mutations. Median number of previous chemotherapy (CT) lines was 4 (3-8). Four patients were with chemo re-sistant relapse post allo-HCT (MSD-1, 10/10 MUD -3) 5-18 months before CAR T-cell infusion. All patients developed CRS (grade 1-3) and were treated with i.v tocili-zumab and dexamethasone. 2/6 patients suffered from ICANS and were treated with steroids. In 4/6 patients, day 28 BM aspiration disclosed normal hematopoie-sis with no excess blasts and lack of t(8;21) by FISH confirming clinical and cyto-genetic remission, while 2/6 pts with progressive AML had no response (Danylesko etal. Abstract EHA 2023, submitted).
Interestingly, other subsets of AML display an aberrant expression of CD19. These observations indicate that CD19 can be a target of choice for CAR-T cells in patients with R/R AML expressing this antigen.
In this study, we plan to offer anti-CD19 CAR-T cell therapy to patients with re-lapsed/refractory AML expressing CD19 for whom no curative alternatives are available.
To this end, CAR-T cells will be manufactured using closed semi-automated bioreactor CliniMACS Prodigy (Miltenyi Biotec) in academic setting.
- Conditions
- Relapsed Adult AML
- Being tested
- CAR-T cell therapy
- Keywords
- Relapsed/refractory AML expressing CD19, AML, CD19, CAR-T cells
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR-T cell therapyDrug
cyclophosphamide and fludarabin conditioning , followed by a target dose of 1 x 10exp6 of autologous, genetically modified, anti-CD19 CAR-T cells per kg of body weight.
| Study group | Role | What they receive |
|---|---|---|
| Experimental group | Other | Not described Receives: Drug: CAR-T cell therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients deceased without progression one month after CAR-T cell infusion
Non-progression mortality (NPM), type and frequency of adverse events. NPM is defined as death occurred in patients without evidence of AML progression. Absence of response, progression or relapse of AML define progression status
Measured: at 1 month
Secondary outcomes (8)
Number of patients with manufacturing failure and out of specification (OOS) deviation
Measured: Througth study completion, an average of 2 years
Duration of CAR-T cell persistence in blood after infusion evaluated by flow-cytometry and PCR,
Measured: Througth study completionan, average of 2 years
Number of patients with overall response
Measured: at 1 month
Response duration
Measured: at 3 months, 6 months and 12 months
Number of patients alive
Measured: at 3 months, 6 months and 12 months
Number of patients alive without relapse
Measured: at 3 months, 6 months and 12 months
Number of deaths without progression
Measured: at 3 months, 6 months and 12 months
Number of patients with complete remission (CR)
Measured: at 1 month and 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2024
- Study start10 Jul 2025
- Primary completion10 Jul 2029 (estimated)
- Study completion10 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed Adult AMLStudies of the same condition, open and under way.
- More trials run by University Hospital, LilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Lille
- Sponsor type
- University, hospital or other
- Collaborators
- Ministry of Health, France, University Hospital, Rouen, Miltenyi
- Responsible party
- Sponsor
- Investigators
- Ibrahim Yakoub-Agha, MD,PhD, Principal investigator, University Hospital, Lille
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06649227
- Sponsor's protocol ID
- 2021_0578
- Other IDs
- 2023-509212-29-01, 2023
- Acronym
- CARLA-M19
- Status last verified
- Nov 2025
- First submitted
- 15 Oct 2024
- Last updated
- 5 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Non-randomized Phase I Study Investigating the Safety of CD19 CAR-T Cells in Patients With Refractory/Relapsed AML Expressing CD19.
- ClinicalTrials.gov ID
- NCT06649227
- Acronym / sponsor ID
- CARLA-M19 / 2021_0578
- Conditions
- Relapsed Adult AML
- Keywords
- Relapsed/refractory AML expressing CD19, AML, CD19, CAR-T cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- University Hospital, LilleUniversity, hospital or other
- Collaborators
- Ministry of Health, France, University Hospital, Rouen, Miltenyi
- Study start
- 10 Jul 2025 (actual)
- Primary completion
- 10 Jul 2029 (estimated)
- Study completion
- 10 Jul 2030 (estimated)
- First posted
- 18 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Refractory/Relapsed (R/R) acute myeloid leukemia (AML) is associated with a dis-mal prognosis.
In some subsets of AML such as AML driven by the t(8;21) translocation, leading to the RUNX1-RUNX1T1 (AML1-ETO) fusion transcript expression, CD19 B-cell antigen is aberrantly expressed on malignant blasts in around 80 % of cases. Interestingly, the expression of the CD19 antigen is also detected in the CD34+ CD38-population leukemic stem cells.
t(8;21) AML subtype has a rather good prognosis with an intensive chemotherapy regimen, but relapses occur in around 40 % of the patients and new therapeutic options are needed for these patients.
Plesa et al, reported a successful treatment of a refractory t(8;21) AML with bispecific monoclonal antibodies that targets CD19. More recently, Danylesko et al, have reported long-term remission following CD19 CAR-T cells in a heavily pre-treated patient with t(8;21) AML(1). The same group has just submitted an abstract of 6 treated patients to the European Haematology Association (EHA) 2023 meet-ing: Six patients (adults-5, child-1) with t(8; 21) AML (confirmed by cytogenetic and FISH) and aberrant CD19 expression were included. One patient had a complex karyotype. Molecular analysis for CKIT, NPM1, IDH1, IDH2, and CBPa were nega-tive in all pts. One pt harbors the FLT3 ITD and TKD mutations. Median number of previous chemotherapy (CT) lines was 4 (3-8). Four patients were with chemo re-sistant relapse post allo-HCT (MSD-1, 10/10 MUD -3) 5-18 months before CAR T-cell infusion. All patients developed CRS (grade 1-3) and were treated with i.v tocili-zumab and dexamethasone. 2/6 patients suffered from ICANS and were treated with steroids. In 4/6 patients, day 28 BM aspiration disclosed normal hematopoie-sis with no excess blasts and lack of t(8;21) by FISH confirming clinical and cyto-genetic remission, while 2/6 pts with progressive AML had no response (Danylesko etal. Abstract EHA 2023, submitted).
Interestingly, other subsets of AML display an aberrant expression of CD19. These observations indicate that CD19 can be a target of choice for CAR-T cells in patients with R/R AML expressing this antigen.
In this study, we plan to offer anti-CD19 CAR-T cell therapy to patients with re-lapsed/refractory AML expressing CD19 for whom no curative alternatives are available.
To this end, CAR-T cells will be manufactured using closed semi-automated bioreactor CliniMACS Prodigy (Miltenyi Biotec) in academic setting.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental group | Other | Drug: CAR-T cell therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Subject is ≥ 18 years of age at the time of signing the informed consent form,
- Patient with AML that expresses CD19 by Flow-cytometry, (CD19 expression ≥ 70% of AML blasts)
- Patients with R/R AML defined as:
- Lack of accessible targeted therapy that has not been previously utilized.
- Eastern Cooperative Oncology Group (ECOG) performance status of < 2,
Key exclusion criteria (16 listed)
- Patient unable to sign the informed consent,
- Patient with R/R AML that does not expresses CD19,
- 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,
- Prior CD19 targeted therapy,
- Prior CAR therapy or other genetically modified T cell therapy,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CAR-T cell therapycyclophosphamide and fludarabin conditioning , followed by a target dose of 1 x 10exp6 of autologous, genetically modified, anti-CD19 CAR-T cells per kg of body weight. | Drug | Experimental group |
Primary outcome
Number of patients deceased without progression one month after CAR-T cell infusion
Time frame: at 1 month
Non-progression mortality (NPM), type and frequency of adverse events. NPM is defined as death occurred in patients without evidence of AML progression. Absence of response, progression or relapse of AML define progression status
8 secondary outcomes
Number of patients with manufacturing failure and out of specification (OOS) deviation
Time frame: Througth study completion, an average of 2 years
Duration of CAR-T cell persistence in blood after infusion evaluated by flow-cytometry and PCR,
Time frame: Througth study completionan, average of 2 years
Number of patients with overall response
Time frame: at 1 month
Response duration
Time frame: at 3 months, 6 months and 12 months
Number of patients alive
Time frame: at 3 months, 6 months and 12 months
Number of patients alive without relapse
Time frame: at 3 months, 6 months and 12 months
Number of deaths without progression
Time frame: at 3 months, 6 months and 12 months
Number of patients with complete remission (CR)
Time frame: at 1 month and 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ibrahim Yakoub-Agha, MD,PhD principal investigator
University Hospital, Lille
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CAR-T cell therapy in people with Relapsed Adult AML, run by University Hospital, Lille at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ibrahim Yakoub-Agha, MD,PhD (0320445962 ext. +33, ibrahim.yakoubagha@chru-lille.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients deceased without progression one month after CAR-T cell infusion (time frame: at 1 month). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2025.