Donor Derived CD117 CAR-T Cells in the Treatment of R/R Acute Myeloid Leukemia

Official title

Donor Derived CD117 CAR-T Cells in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Overview

A Clinical Study on the Safety and Effectiveness of Donor Derived CD117 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 CD117 CAR-T Cell in patients with relapsed or refractory acute myeloid leukemia. It is planned to enroll 15-50 participants in this trial.

Interventions

• Biological CD117 CAR T-cells
  Each subject receive CD117 CAR T-cells by intravenous infusion

Primary outcome measures

• Dose-limiting toxicity (DLT) [Time frame: Up to 28 days after Treatment]
• Incidence of treatment-emergent adverse events (TEAEs) [Time frame: Up to 2 years after Treatment]

Secondary outcome measures (4)

• Complete response (CR), and complete response with incomplete hematologic recovery (CRi) [Time frame: Up to 12 weeks after CAR-T infusion]
• Duration of remission ,DOR [Time frame: Up to 1 years after CAR-T infusion]
• Overall survival, OS [Time frame: Up to 1 years after CAR-T infusion]
• Leukemia-Free Survival, LFS [Time frame: Up to 2 years after Treatment]

Eligibility criteria

Inclusion criteria

• 1\. Patients with a histologically or immunophenotypically confirmed diagnosis of CD117-positive Acute Myeloid Leukemia (AML).
• 2\. Diagnosis must meet the 2016 WHO classification criteria for AML and fulfill the definitions for relapsed or refractory disease per the \*Chinese Guidelines for the Diagnosis and Management of Relapsed/Refractory Acute Myeloid Leukemia (2017 Edition)\*, with no available suitable standard therapeutic options or registered clinical trials.
• a). Relapsed AML: Defined as the reappearance of leukemic blasts in the peripheral blood, bone marrow blast count >5% (when assessed morphologically, after excluding regenerative changes post-consolidation chemotherapy), or development of extramedullary disease after achieving a Complete Remission (CR).
• b). Refractory AML (meeting at least one criterion): Failure to achieve CR following two cycles of standard induction therapy in newly diagnosed patients; relapse within 12 months after CR following consolidation therapy; relapse beyond 12 months that fails to respond to conventional salvage chemotherapy; ≥2 relapses; or persistent extramedullary leukemia.
• 3\. Presence of >5% bone marrow blasts (by morphology) and/or >1% (by flow cytometric analysis).
• 4\. Total bilirubin ≤1.5 × ULN (≤51 μmol/L) ALT and AST ≤3 × ULN Serum creatinine ≤1.5 × ULN (≤176.8 μmol/L)
• 5\. Left ventricular ejection fraction (LVEF) ≥50% as assessed by echocardiography.
• 6\. Oxygen saturation ≥92% on room air.
• 7\. Life expectancy ≥3 months.
• 8\. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
• 9\. For patients of childbearing potential: Agreement to use highly effective contraception from screening, throughout the study treatment period, and for at least 6 months after the cell infusion (due to unknown risks to the fetus).
• 10\. Voluntary participation, understanding of the study procedures, and provision of written informed consent by the patient or their legally authorized representative.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The first affiliated hospital of medical college of zhejiang university — Hangzhou

Identifiers

NCT: NCT07144020 · TXB2024010

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗