Study to Evaluate the Safety and Preliminary Efficacy of CLL1 and CD38 Dual CAR-T in r/r AML

NCT06110208 | Terminated Early Phase 1

• 1 other identifier: GC12-132
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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) .

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Dose limited toxicity (DLT);

  Dose limited toxicity (DLT);

  28 days after CAR-T infusion

• Adverse events (AE)

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

  48 weeks after CAR-T infusion

Secondary Outcomes (14)

• • 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

• • Partial response rate (PRR);

  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

• • Median bone marrow blast percentage decline;

  1month, 2 months, 3months, 6months ,9months,12months after CAR-T infusion

Other Outcomes (4)

• • Explore the correlation between serum cytokines, Cytokine Release Syndrome (CRS) and neurotoxicity after infusion of CLL1 and CD38 dual-target CAR-T injection;

  Days 4, 7, 10, 14 ,21,28 and months 2, 3, 6, 9, 12 after Fast Dual CAR-T infusion

• • Explore the correlation between the number of CAR-T cells in the blood/bone marrow/tumor tissue of subjects and CRS and neurotoxicity after infusion of CLL1 and CD38 dual-target CAR-T injection;

  Days 4, 7, 10, 14 ,21,28 and months 2, 3, 6, 9, 12 after Fast Dual CAR-T infusion

• • Explore the correlation between CAR copy number and CRS and neurotoxicity in the blood/bone marrow/tumor tissue of subjects after infusion of CLL1 and CD38 dual-target CAR-T injection;

  Days 4, 7, 10, 14 ,21,28 and months 2, 3, 6, 9, 12 after Fast Dual CAR-T infusion

Study Arms (1)

AML subjects

EXPERIMENTAL

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) .

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

Interventions

CLL1 and CD38 dual-target CAR-T injection DRUG

CLL1 and CD38 dual-target CAR-T injection

AML subjects

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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);
• Serum creatinine clearance \>45mL/min (calculated according to the Cockcroft-Gault formula);
• Left ventricular ejection fraction ≥35%;
• Basic oxygen saturation in indoor air environment is ≥ 92 %
• Ability to discontinue corticosteroids (dexamethasone ≥3 mg/day or other equivalent doses of steroids) starting on day -7 and continuing until 30 days after CAR-T cell infusion;
• Women of childbearing age must have a negative pregnancy test for human chorionic gonadotropin (HCG) (immunofluorescence method) during the screening period and baseline period. Male subjects will need to agree not to donate sperm for at least one year after reinfusion. Males and sexual partners of childbearing potential agree to use highly effective contraceptive measures for at least 1 year after infusion;

You may not qualify if:

• 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;
• A history of clinically significant ventricular arrhythmia or syncope of unknown origin (not caused by vasovagal or dehydration);
• Have a history of severe non-ischemic cardiomyopathy;
• Cardiac dysfunction (left ventricular \<35%) assessed by echocardiography or multiple gated acquisition scans, or other heart disease with clinical symptoms within 6 months before enrollment;
• Active or previous central nervous system involvement, or clinically significant clinical manifestations of central nervous system involvement in subjects with acute myeloid leukemia ;
• A positive virological test result for any of the following:

Sponsors & Collaborators

• 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China: lead
• Gracell Biotechnologies (Shanghai) Co., Ltd.: collaborator

Study Sites (1)

920th Hospital of Joint LogisticsSupport Force of People's Liberation

Kunming, Yunnan, 650000, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Sanbin Wang

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2023
• First Posted: October 31, 2023
• Study Start: October 10, 2023
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: February 26, 2025

Record last verified: 2025-02

Locations

CN (1)