A Clinical Study to Explore the Safety and Efficacy of CD33 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia

A Clinical Study on the Safety and Effectiveness of targeting CD33 CAR-T Cell in the treatment of Relapsed/Refractory Acute Myeloid Leukemia

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Biological: CD33 CAR T-cells

Detailed Description

This is a single-arm, open-label, dose-escalation clinical trial to evaluate the safety and efficacy of CD33 CAR-T Cell in patients with relapsed or refractory acute myeloid leukemia. It is planned to enroll 15-27 participants in this trial.

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: He Huang, MD; Phone Number: 057187233772; Email: hehuangyu@126.com
• Study Contact Backup: Name: Yongxian Hu, MD; Phone Number: 057187233772; Email: huyongxian2000@aliyun.com

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Recruiting
      • The first affiliated hospital of medical college of zhejiang university
      • Contact: He Huang, MD; Phone Number: 057187233772; Email: hehuangyu@126.com
      • Contact: Yongxian Hu, MD; Phone Number: 057187233772; Email: huyongxian2000@aliyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Male or female, age ≥ 18 years old;
• 2. CAR-T cells can be prepared normally, or who have failed to prepare autologous CAR-T cells (including the number of autologous lymphocytes <1×10^9 or the expansion during the preparation process is insufficient or cannot reinfusion);
• 3. Patients diagnosed with CD33 positive acute myeloid leukemia (AML) through histological or immunological examination，and CD33 positive expression rate >80%;
• 4. Complies with the 2016 WHO classification for AML diagnosis and meets the diagnostic criteria for recurrence and refractory acute myeloid leukemia in the "Chinese Guidelines for the Diagnosis and Treatment of relapsed and refractory acute myeloid leukemia (2017 edition)", and currently there are no clinically relevant treatments or suitable clinical trials for registration:
• a) Diagnostic criteria for recurrent AML: After complete remission (CR), leukemia cells reappear in peripheral blood or primitive cells in bone marrow>0.050 (excluding other reasons such as bone marrow regeneration after consolidation chemotherapy) or leukemia cell infiltration appears outside the bone marrow;
• b) Diagnostic criteria for refractory AML: initial treatment cases that have failed to respond to two courses of standard protocol treatment; Patients who relapse within 12 months after consolidation and intensive treatment after CR; Patients who relapse after 12 months but fail conventional chemotherapy; Patients with 2 or more relapses; Persistent extramedullary leukemia;
• 5. The number of primitive cells (promyelocytes and/or promyelocytes) in the bone marrow > 5% (morphology) and/or > 1% (flow cytometry detection);
• 6. Total bilirubin ≤ 51 μmol / L, ALT and AST ≤ 3 times of the upper limit of normal value, serum creatinine ≤ 176.8 μmol / L；
• 7. Echocardiography shows left ventricular ejection fraction (LVEF) ≥ 50%;
• 8. There is no active pulmonary infection, and the oxygen saturation during air inhalation is more than 92%;
• 9. The estimated survival time is more than 3 months;
• 10. ECOG score was 0-2;
• 11. Pregnant/lactating women, or male or female patients who have fertility and are willing to take effective contraceptive measures at least 6 months after the last cell infusion during the study period;
• 12. Those who voluntarily participated in this trial and provided informed consent;

Exclusion Criteria:

• 1. Patients with the history of epilepsy or other CNS disease;
• 2. Patients with prolonged QT interval time or severe heart disease;
• 3. Active infection with no cure;
• 4. Active infection of hepatitis B virus or C virus ;
• 5. Before using any gene therapy products;
• 6. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal;
• 7. Suffering from other uncontrolled diseases that the researchers consider unsuitable for joining;
• 8. Infected with AIDS virus;
• 9. Any situation that researchers believe may increase the risk to the subjects or interfere with the trial results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAR-T cells（ chimeric antigen receptor T cells）; Dose escalation follows the standard 3+3 dose escalation design. A total of 3 dose levels are set for subjects.	Biological: CD33 CAR T-cells; Each subject receive CD33 CAR T-cells by intravenous infusion; Other Names: CD33 CAR T-cells injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-emergent adverse events (TEAEs)	Incidence of treatment-emergent adverse events [Safety and Tolerability]	Up to 2 years after Treatment
Dose-limiting toxicity (DLT)	Adverse events assessed according to NCI-CTCAE v5.0 criteria	Up to 28 days after Treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival, OS	The time from CAR-T infusion to death due to any cause	Up to 1 years after CAR-T infusion
Duration of remission ,DOR	The time from CR/CRi and PR to disease relapsed or death due to disease progression after CAR-T infusion	Up to 1 years after CAR-T infusion
Complete response (CR), and complete response with incomplete hematologic recovery (CRi)	The proportion of patients with CR (complete response) /CRi (complete response with incomplete blood cell recovery) and PR (partial response).	Up to 12 weeks after CAR-T infusion
Leukemia-Free Survival, LFS	The time from CAR-T infusion torecurrence or metastasis	Up to 2 years after Treatment

Collaborators and Investigators

• Sponsor: Zhejiang University
• Collaborators: Yake Biotechnology Ltd.
• Investigators: Principal Investigator: He Huang, MD, First Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): January 10, 2025
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2027

Study Registration Dates

• First Submitted: January 1, 2025
• First Submitted That Met QC Criteria: January 1, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 1, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: CD33 CAR-T
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: TXB2024025

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No