Using CD7 CAR-T cells to treat relapsed or refractory acute leukemia

Clinical Study on the Safety and Efficacy of CD7 CAR-T Cell in Patients With Relapsed/Refractory Acute Leukemia

This study is testing a new type of CAR-T cell therapy to see if it can help people with relapsed or hard-to-treat acute leukemia feel better and improve their chances of survival.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 200 (estimated)
• Ages: 14 Years to 65 Years
• Sex: All
• Sponsor: The General Hospital of Western Theater Command (Academic / other)
• Drugs / interventions: ipilimumab, chemotherapy, CAR-T, CAR T
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT06585345 on ClinicalTrials.gov

What this trial studies

This clinical study evaluates the safety and efficacy of CD7 CAR-T cell therapy in patients with relapsed or refractory acute leukemia. It is an open-label, single-arm, single-center trial where patients will receive escalating doses of CD7 CAR-T cells, starting from a low dose and increasing based on tolerance. The study aims to assess various outcomes, including complete and partial response rates, recurrence rates, and overall survival over a period of up to five years. Adverse events will also be monitored to ensure patient safety throughout the treatment process.

Who should consider this trial

Good fit: Ideal candidates are patients aged 14 and older diagnosed with acute leukemia who have not responded to conventional chemotherapy.

Not a fit: Patients with acute leukemia who are in complete remission or those who have not undergone prior systemic treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with limited alternatives for relapsed or refractory acute leukemia.

How similar studies have performed: Other studies using CAR-T cell therapies have shown promising results, indicating potential success for this novel approach.

Eligibility criteria

Inclusion Criteria:

1. Patients diagnosed with acute leukemia.
2. Acute leukemia complex/refractory cases with poor response to conventional chemotherapy: 1) patients who did not achieve complete remission after 2 courses of treatment with standard induced remission regimen; 2) Recurrence within 6 months after the first remission; 3) Relapse 6 months after the first remission, but failure to be treated again with the original induced remission regimen; 4) Recurrent patients.
3. At least 2 weeks or 5 half-lives (whichever is shorter) from the start of preconditioning chemotherapy after prior systemic treatment, except for immune checkpoint inhibitors/agonists; Systemic immune checkpoint inhibitor/agonist treatment is at least 3 half-lives away from pre-treatment chemotherapy (e.g., ipilimumab, etc.).
4. Toxic reactions caused by previous antitumor therapy must be stabilized and returned to ≤ grade 1 (except for clinically insignificant toxicity, such as baldness).
5. Over 14 years old, under 65 years old.
6. Physical Strength score 0-3 (ECOG standard)
7. No obvious active infection or graft-versus-host disease
8. Expected survival ≥3 months
9. Adequate kidney, liver, lung and heart function, defined as:

   Creatinine clearance (estimated by Cockcroft Gault formula) \> 60 mL/min; Serum ALT/AST ≤ 2.5 ULN; Total bilirubin ≤1.5 ULN, excluding subjects with Gilbert's syndrome; Cardiac ejection fraction ≥ 50%, echocardiography confirmed centropericardial effusion, and ECG showed no clinically significant abnormal findings.

   There was no clinically significant pleural effusion. Baseline blood oxygen saturation under indoor ventilation was \> 92%.
10. The serum pregnancy test results of fertile women must be negative (women who have undergone surgical sterilization or at least 2 years after menopause are considered to be infertile).

Exclusion Criteria:

1. The subject has had other malignancies, non-melanoma skin tumors, carcinoma in situ (e.g. Cervix, bladder, breast), unless disease-free survival of at least 3 years
2. Presence or suspicion of uncontrollable fungal, bacterial, viral or other infections.
3. Known human immunodeficiency virus (HIV) infection
4. Known history of hepatitis B (HBsAg positive) or hepatitis C (HCV antibody positive). Subjects with latent or prehepatitis B infection (defined as HBcAb positive and HBsAg negative) can be enrolled only if PCR tests for HBV DNA are negative. In addition, these subjects were required to undergo a monthly PCR test for HBV DNA. Participants who are serologically positive for HCV antibodies can also be enrolled if their PCR test results for HCV RNA are negative.
5. Existing or past CNS disease, such as seizures, cerebrovascular ischemia/bleeding, dementia, cerebellar disease, or any CNS-related autoimmune disease
6. Subjects with severe heart disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months prior to screening, or any grade 3 (moderate) or 4 (severe) heart disease (according to the New York Heart Society Functional Grading Method NYHA) with lymphoma infiltrating the heart's atria or ventricles
7. A history of myocardial infarction, angioplasty or stent placement, unstable angina pectoris, or other clinically significant heart disease in the 12 months prior to enrollment
8. Emergency treatment is expected or likely to occur within 6 weeks due to rapid tumor progression (e.g. tumor mass compression)
9. Primary immune deficiency
10. History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months prior to enrollment
11. Any medical condition that may affect the evaluation of safety or efficacy
12. Have had severe rapid hypersensitivity reactions to any of the drugs to be used in this study
13. Administer live vaccine within ≤6 weeks prior to initiation of the pretreatment regimen
14. Pregnant or lactating female subjects
15. Male or female subjects who do not consent to effective contraception from the time they sign informed consent until 6 months after completing AT19 treatment
16. Subjects judged by the investigator had difficulty completing all visits or procedures required by the study protocol (including follow-up visits), or were not compliant enough to participate in the study
17. In the past 2 years, subjects have had other malignancies, non-melanoma skin tumors, carcinoma in situ (e.g. Cervix, bladder, breast), end-organ damage due to autoimmune diseases (e.g. Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), or need to systematically administer immunosuppressive or other drugs for systemic disease control. Unless disease free survival of at least 3 years
18. Participate in other clinical experimenters during the same period

Where this trial is running

Chengdu, Sichuan

• The General Hospital of Western Theater Command — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: Hai Yi, Ph.D — The General Hospital of Western Theater Command
• Study coordinator: Hai Yi, Ph.D

Conditions Acute-Leukemia; Relapsed; Refractory