Clinical trial NCT06762132: A Clinical Study to Explore the Safety and Efficacy of CD33 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia
Official title: A Clinical Study to Explore the Safety and Efficacy of CD33 CAR-T Cell in Relapsed/Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Acute Myeloid Leukemia
Keywords: CD33 CAR-T
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2025-01-07
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Up to 28 days after Treatment
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years after Treatment
Secondary outcomes:
measure: Complete response (CR), and complete response with incomplete hematologic recovery (CRi)
timeFrame: Up to 12 weeks after CAR-T infusion
measure: Duration of remission ,DOR
timeFrame: Up to 1 years after CAR-T infusion
measure: Overall survival, OS
timeFrame: Up to 1 years after CAR-T infusion
measure: Leukemia-Free Survival, LFS
timeFrame: Up to 2 years after Treatment
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first affiliated hospital of medical college of zhejiang university
state: Zhejiang
Study officials:
affiliation: First Affiliated Hospital of Zhejiang University
name: He Huang, MD
role: PRINCIPAL_INVESTIGATOR
References: