Sequential CAR-T Cells Targeting CD33/CD123 in Patients With Acute Myelocytic Leukemia AML

Phase 1

Recruiting

• Conditions: Acute Myeloid Leukemia; AML; AML, Adult; AML, Adult Recurrent
• Interventions: Biological: CD123/CD33 CART

• Registration Number: NCT06420063
• Lead Sponsor: Essen Biotech

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.

Study Timeline

• Study First Submitted: 2024-05-14
• Study First Submitted QC: 2024-05-14
• Study First Posted: 2024-05-17
• Study Start: 2024-07-10
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-10
• Last Update Posted: 2024-11-12
• Primary Completion: 2025-12-10
• Study Completion: 2026-12-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 85

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (CD33/CD123 CAR T cells, chemotherapy)	CD123/CD33 CART	Patients will be administered fludarabine phosphate intravenously (IV) over a 30-minute period on days -4 to -2. Additionally, cyclophosphamide will be administered intravenously (IV) over 60 minutes on day -2. Subsequently, patients will receive CD33/123 CAR T cells intravenously (IV) over a duration of 10-20 minutes on day 0. Patients who exhibit positive responses to the initial dose of CD33/123 CAR T cells, do not experience unacceptable side effects, and have a sufficient quantity of cells available may be eligible to receive 2 or 3 additional doses of CD33/CD123 CAR T cells.

Primary Outcome Measures

Name	Time	Method
Incidence and severity of dose-limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD5/CD7 chimeric antigen receptor (CAR) T cells	28 days	Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 at three dose levels until the maximum tolerated dose (MTD) is determined.

Secondary Outcome Measures

Name	Time	Method
Rate of successful manufacture and expansion of the CD33/123 chimeric antigen receptor (CAR) T cells	10-14 days	satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis (COA)

Trial Locations

Locations (1)

District One Hospital; 🇨🇳 Beijing, Beijing, China