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

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

NCT ID: NCT06420063

Condition: AML
Acute Myeloid Leukemia
AML, Adult Recurrent
AML, Adult

Conditions: Official terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute

Conditions: Keywords:
aml
cd33
cd123
CAR-T

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

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

Masking: None (Open Label)

Masking description: Open-label clinical trials are a category of clinical research where the masking is minimal or nonexistent. In such trials, both the participants and the researchers are fully aware of the treatment assignments, which means participants know the treatment they are receiving, and researchers are aware of each participant's treatment group.

Intervention:

Intervention type: Biological
Intervention name: CD123/CD33 CART
Description: The intervention in this clinical trial involves a novel approach using CD22/123-Chimeric Antigen Receptor T (CAR T) cells combined with chemotherapy. The goal is to assess safety and efficacy in patients with specific hematologic malignancies. Treatment Regimen: Patients in the trial will undergo the following regimen: Fludarabine Phosphate (Days -4 to -2): IV administration of fludarabine phosphate over 30 minutes on days -4 to -2. It's part of the preparatory regimen to enhance the body's response to CAR T-cell therapy. Cyclophosphamide (Day -2): IV cyclophosphamide over 60 minutes on day -2. CD33/123-Chimeric Antigen Receptor T Cells (Day 0): IV administration of investigational therapy, CD33/123-CAR T cells, over 10-20 minutes on day 0. Additional Doses: Eligible patients responding well to the initial CD33/123 CAR-T cell infusion without unacceptable side effects and sufficient CAR T cell availability may receive 2 or 3 additional doses.
Arm group label: Treatment (CD33/CD123 CAR T cells, chemotherapy)

Other name: EB-BH2025

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.

Criteria for 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.

Gender: All

Minimum age: 6 Years

Maximum age: 90 Years

Healthy volunteers: No

Locations:

Facility:
Name: District One Hospital

Address:
City: Beijing
Zip: 086-373
Country: China

Status: Recruiting

Contact:
Last name: SAMI XI, dr

Phone: +14012275001
Email: SFM@districtonehospital.com

Start date: July 10, 2024

Completion date: December 28, 2026

Lead sponsor:
Agency: Essen Biotech
Agency class: Other

Source: Essen Biotech

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06420063