Study Investigating the Safety of CD19 CAR-T Cells in Relapsed/Refractory AML Expressing CD19

NCT06649227 | Recruiting Phase 1 DMC

• 2 other identifiers: 2021_05782023-509212-29-01
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Relapsed Adult AML

Keywords

Relapsed/refractory AML expressing CD19; AML; CD19; CAR-T cells

Outcome Measures

Primary Outcomes (1)

• 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

  at 1 month

Secondary Outcomes (8)

• Number of patients with manufacturing failure and out of specification (OOS) deviation

  Througth study completion, an average of 2 years

• Duration of CAR-T cell persistence in blood after infusion evaluated by flow-cytometry and PCR,

  Througth study completionan, average of 2 years

• Number of patients with overall response

  at 1 month

• Response duration

  at 3 months, 6 months and 12 months

• Number of patients alive

  at 3 months, 6 months and 12 months

Study Arms (1)

Experimental group

OTHER

Drug: CAR-T cell therapy

Interventions

CAR-T cell therapy DRUG

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.

Experimental group

Eligibility Criteria

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

You may qualify if:

• 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.
• 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),

You may not qualify if:

• 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,
• 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,

Sponsors & Collaborators

• University Hospital, Lille: lead
• Miltenyi: collaborator
• Ministry of Health, France: collaborator
• University Hospital, Rouen: collaborator

Study Sites (1)

CHU de Lille

Lille, 59000, France

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

Immunotherapy, Adoptive

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

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Ibrahim Yakoub-Agha, MD,PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ibrahim Yakoub-Agha, MD,PhD

CONTACT

0320445962; ibrahim.yakoubagha@chru-lille.fr

Study Design

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

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 18, 2024
• Study Start: July 10, 2025
• Primary Completion (Estimated): July 10, 2029
• Study Completion (Estimated): July 10, 2030
• Last Updated: December 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)