Clinical Study to Evaluate the Safety and Preliminary Efficacy of CLL1 and CD38 Dual CAR-T Injection in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia

920th Hospital of Joint Logistics Support Force of People's Liberation Army of China1 site in 1 country3 target enrollmentOctober 10, 2023

ConditionsAcute Myeloid Leukemia

InterventionsCLL1 and CD38 dual-target CAR-T injection

Overview

Phase: Early Phase 1
Intervention: CLL1 and CD38 dual-target CAR-T injection
Conditions: Acute Myeloid Leukemia
Sponsor: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Enrollment: 3
Locations: 1
Primary Endpoint: Dose limited toxicity (DLT);
Status: Terminated
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study is a single-center clinical study. The main purpose is an IIT clinical trial to evaluate the safety and preliminary efficacy of CLL1 and CD38 dual CAR-T injection in r/r AML subjects . The included population were patients with relapsed and refractory acute myeloid leukemia (r/r AML) .

Detailed Description

Single-center clinical study. The main purpose is an IIT clinical trial to evaluate the safety and preliminary efficacy of CLL1 and CD38 dual CAR-T injection in r/r AML subjects . The included population was patients with relapsed and refractory acute myeloid leukemia (r/r AML) .

Registry

clinicaltrials.gov

Start Date

October 10, 2023

End Date

July 1, 2024

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•18-70 years old (including the critical value) when signing the informed consent form;
•Diagnosed with acute myeloid leukemia (excluding APL) according to the World Health Organization 2016 criteria and relapsed and refractory AML according to the ELN2022 criteria;
•Positive expression of CLL1 and/or CD38 in malignant cells must be detected by immunohistochemistry or flow cytometry (≥20 % );
•If there are AEs caused by previous chemotherapy, it must be restored to CTCAE V5.0 grade 1;
•Estimated survival time ≥3 months;
•ECOG score 0 or 1 during screening period;
•Hemoglobin ≥80g/L (have not received red blood cell transfusion within 7 days before screening, use of recombinant human erythropoietin is allowed);
•Adequate organ functional reserve:
•Alanine aminotransferase/aspartate aminotransferase ≤2.5× ULN (upper limit of normal value);
•Serum total bilirubin ≤2× ULN, except for subjects with congenital bilirubinemia (for subjects with Gilbert syndrome, direct bilirubin needs to be ≤1.5× ULN);

Exclusion Criteria

•Diagnosis of acute promyelocytic leukemia;
•clinical trial investigational drugs or cell therapies within 2 weeks or 5 half-lives ;
•Acute myeloid leukemia of unknown lineage ;
•Those who have active graft-versus-host disease (GVHD) at the time of enrollment or develop active acute or chronic GVHD within 4 weeks after enrollment or require immunosuppressive drugs to treat GVHD;
•There is an active infection;
•Suffering from other malignant tumors (except non-melanoma skin cancer and in situ cervical cancer, bladder cancer, and breast cancer with a disease-free survival period of more than 5 years);
•The subject has had a stroke or epilepsy within 6 months before signing the informed consent form;
•The subjects' cardiac function showed the following conditions:
•New York Heart Association (NYHA) class III or IV heart failure;
•Myocardial infarction or coronary artery bypass grafting (CABG) occurred within 6 months before signing the informed consent form;

Arms & Interventions

AML subjects

This study is a single-center clinical study. The main purpose is an IIT clinical trial to evaluate the safety and preliminary efficacy of CLL1 and CD38 dual CAR-T injection in r/r AML subjects . The included population was patients with relapsed and refractory acute myeloid leukemia (r/r AML) .

Intervention: CLL1 and CD38 dual-target CAR-T injection

Outcomes

Primary Outcomes

Dose limited toxicity (DLT);

Time Frame: 28 days after CAR-T infusion

Dose limited toxicity (DLT);

Adverse events (AE)

Time Frame: 48 weeks after CAR-T infusion

• Adverse events (AE): CTCAE version 5.0 standards will be used for rating

Secondary Outcomes

• Partial response rate (PRR);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
• Median bone marrow blast percentage decline;(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
• CR with incomplete hematologic recovery rate (CRiR);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
• Overall response rate (ORR);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
• Overall complete response rate (CRR);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
• Event-free survival (EFS);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
• Relapse-free survival (RFS);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
• Overall survival (OS);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
• Expansion and persistence of CAR-T cells (CAR copy number and CAR - T cell number)(Days 4, 7, 10, 14 ,21,28 and months 2, 3, 6, 9, 12 after Fast Dual CAR-T infusion)
• The proportion of subjects with RCL detected in peripheral blood and the insertion site of CAR-T cell lentivirus within 15 years after the infusion of CLL1 and CD38 dual-target CAR-T injection.(within 15 years after the infusion of CLL1 and CD38 dual CAR-T injection)
• Morphologic leukemia-free state rate (MLFSR);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
• The proportion of patients who achieved complete remission (CR) who tested negative for MRD (MRD-rate);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
• Duration of response (DOR);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)
• CR with partial hematologic recovery rate (CRhR);(1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion)