Clinical trial NCT06420063: Sequential CAR-T Cells Targeting CD33/CD123 in Patients With Acute Myelocytic Leukemia AML
Official title: Sequential CAR-T Cell Infusion Targeting CD33 and CD123 for Refractory/Relapsed Acute Myeloid Leukaemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: AML
Acute Myeloid Leukemia
AML, Adult Recurrent
AML, Adult
Keywords: aml
cd33
cd123
CAR-T
Lead sponsor: Essen Biotech
Sponsor class: OTHER
First posted: 2024-05-17
Enrollment: 85
Sex: ALL
Minimum age (years): 6
Maximum age (years): 90
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients enrolled in this clinical trial will receive a carefully designed treatment regimen. Before the infusion of CD33 and CD123 CAR-T cells, participants will undergo preconditioning chemotherapy. This chemotherapy serves to create an optimal environment for CAR-T cell therapy to effectively target and eliminate malignant B cells. Following chemotherapy, participants will receive the infusion of CD33 and CD123 CAR-T cells.
Primary purpose: TREATMENT

Brief summary: This is an open, single-arm, clinical study to evaluate the efficacy and safety of chimeric antigen receptor T cell immunotherapy (CAR-T) targeting CD33 or CD123 or both sequentially in the treatment of Acute Myelocytic Leukemia.

Detailed description: Chimeric antigen receptor (CAR)-modified T cells targeted against CD19 have demonstrated unprecedented successes in treating patients with hematopoietic and lymphoid malignancies. Besides CD19, many other molecules such as CD22, CD30,BCMA,CD123, etc. may have the potential to develop the corresponding CAR-T cells to treat patients whose tumors express those markers. In this study, investigators will evaluate the safety and efficacy of CAR-T targeting CD33/CD123 in patients with Acute Myelocytic Leukemia. The primary goal is safety assessment including cytokine storm response and any other adverse effects. In addition, disease status after treatment will also be evaluated.

The purpose of this clinical trial is to assess the feasibility, safety, and efficacy of multiple CAR T-cell therapy which combines CAR T cells against AML Cells with CAR T cells targeting CD123 or CD33 in patients with relapsed and refractory AML. The study also aims to learn more about the function of CAR T cells and their persistence in AML patients.

Eligibility criteria: Inclusion Criteria:

* Subjects with acute myeloid leukemia who voluntarily signed informed consent and met the following criteria:
* Age older than 6 months.
* Confirmed expression of CLL-1, CD123 and/or CD33 in blast AML by immuno-histochemical staining or flow cytometry.
* Karnofsky performance status (KPS) score is higher than 80 and life expectancy \> 3 months.
* Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: cardiac ejection fraction ≥ 50%, oxygen saturation ≥ 90%, creatinine ≤ 2.5 × upper limit of normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal, total bilirubin ≤ 2.0mg/dL.
* Hgb≥80g/L.
* No cell separation contraindications.
* Abilities to understand and the willingness to provide written informed consent.

Exclusion Criteria:

* Severe illness or medical condition, which would not permit the patient to be managed according to the protocol, including active uncontrolled infection.
* Active bacterial, fungal or viral infection not controlled by adequate treatment.
* Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
* Pregnant or nursing women may not participate.
* Use of glucocorticoid for systemic therapy within one week prior to entering the trial.
* Patients, in the opinion of investigators, may not be able to comply with the study.

Primary outcomes:
measure: Incidence and severity of dose-limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD5/CD7 chimeric antigen receptor (CAR) T cells
timeFrame: 28 days
Secondary outcomes:
measure: Rate of successful manufacture and expansion of the CD33/123 chimeric antigen receptor (CAR) T cells
timeFrame: 10-14 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: District One Hospital
state: Beijing
Study officials:
References: