Treatment of relapsed/refractory multiple myeloma with ESO-T01

Clinical Study for Evaluating ESO-T01 Injection's Safety and Efficacy in Treating Relapsed/refractory Multiple Myeloma

This study is testing a new CAR T-cell therapy called ESO-T01 to see if it can help people with relapsed or refractory multiple myeloma feel better.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Tongji Hospital (Academic / other)
• Drugs / interventions: Tocilizumab, radiation
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT06791681 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of ESO-T01, a novel CAR T-cell therapy, in patients with relapsed or refractory multiple myeloma. The study is designed as a single-center, open-label, dose-escalation trial, where participants will receive varying doses of ESO-T01 after pre-infusion prophylaxis. Patients will be monitored for safety, tolerability, and preliminary efficacy over a two-year follow-up period. The trial aims to determine the pharmacokinetics and pharmacodynamics of the treatment in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with relapsed or refractory multiple myeloma who have undergone at least two prior lines of therapy.

Not a fit: Patients who have not been previously treated for multiple myeloma or those with non-measurable disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with limited treatment alternatives for multiple myeloma.

How similar studies have performed: Other studies utilizing CAR T-cell therapies for multiple myeloma have shown promising results, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years；
2. Diagnosis of multiple myeloma (MM) confirmed according to the IMWG diagnostic criteria, with BCMA expression on MM cells determined by flow cytometry or immunohistochemistry;
3. Previously treated with at least 2 lines of anti-MM therapy, with at least 1 complete treatment cycle for each line, and disease progression within 12 months after the most recent anti-myeloma treatment, or being refractory to both immunomodulatory drugs and proteasome inhibitors, along with disease progression within 2 months after the most recent anti-myeloma treatment (according to the IMWG diagnostic criteria);
4. Disease must be measurable at screening, meeting at least one of the following criteria:Serum M-protein level ≥ 0.5 g/dL; Urinary M-protein level ≥ 200 mg/24h; Serum involved free light chain ≥ 10 mg/dL and an abnormal serum free light chain κ/λ ratio;
5. ECOG score 0-2, with an expected survival time ≥ 3 months;
6. Bone marrow function at screening (or within 2 months prior to screening) meets the following criteria: a.Hemoglobin ≥ 6 g/dL (no red blood cell transfusion within 1 week before screening), recombinant human erythropoietin is allowed; for patients who meet the ≥6 g/dL criterion at screening, red blood cell transfusion is allowed to maintain hemoglobin ≥ 6 g/dL; b.Absolute neutrophil count (ANC) ≥ 600/μL (no use of granulocyte colony-stimulating factor (G-CSF) within 1 week or pegylated G-CSF within 2 weeks prior to screening); c. Platelet count ≥ 50,000/μL; d. Lymphocyte count ≥ 500/μL; e. Absolute CD3-positive T cell count ≥ 150/μL;
7. Renal function at screening (or within 2 months prior to screening) should be normal, with a creatinine clearance ≥ 45 mL/min;
8. Liver function at screening (or within 2 months prior to screening) must meet the following criteria: a. Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 3.0 × the upper limit of normal (ULN); b. Total bilirubin (TBIL) and alkaline phosphatase (AKP or ALP) ≤ 2.0 × ULN (except for congenital hyperbilirubinemia, such as Gilbert's syndrome, where direct bilirubin can be ≤ 1.5 × ULN); c. Albumin ≥ 3 g/dL;
9. Cardiac function at screening (or within 2 months prior to screening) must meet the following criteria: a. Left ventricular ejection fraction ≥ 40% (measured by echocardiogram or MUGA scan); b. No clinically significant pericardial effusion detected; c. No clinically significant ECG abnormalities detected;
10. Pulmonary function at screening (or within 2 months prior to screening) must meet the following criteria: Oxygen saturation ≥ 90%;No clinically significant pleural effusion detected;
11. For women of childbearing potential, a negative pregnancy test must be obtained at screening and prior to drug infusion, and they must not be breastfeeding;
12. Male and female subjects of childbearing potential must agree to use effective contraception from the time of informed consent until 1 year after the study drug administration;
13. Male and female subjects of childbearing potential must agree not to donate sperm or eggs (oocytes) or other reproductive cells from the time of informed consent until 1 year after the study drug administration;
14. The participant or their legally authorized representative must provide written informed consent (ICF), indicating their understanding of the purpose and procedures of the study and their willingness to participate.

Exclusion Criteria:

1. Previous anticancer treatment (as determined by the investigator): a. Received targeted therapy, epigenetic therapy, other investigational drugs, or treatment using invasive investigational medical devices within 5 half-lives; b. Received immune/non-immune-directed systemic therapy within 1 week; Received cytotoxic therapy within 1 week; c. Received proteasome inhibitors or immunomodulatory agent therapy within 2 weeks; d. Received radiotherapy within 4 weeks (if the radiation field covered ≤5% of bone marrow reserve, the subject is eligible regardless of the date of radiotherapy completion);
2. Received allogeneic HSCT within 6 months prior to infusion, or autologous HSCT within 3 months prior to infusion;
3. Other malignancies prior to screening (except the following): Malignancies treated with curative intent and no evidence of active disease ≥2 years before enrollment; Adequately treated non-melanoma skin cancer with no evidence of disease;
4. Previously treated with any viral therapy using VSVG pseudotype virus;
5. Serious uncontrolled infections during screening: Bacterial, viral, fungal, etc. infections;
6. Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with elevated peripheral blood HBV DNA levels within 6 months prior to infusion; Positive for hepatitis C antibody (HCV Ab) with elevated peripheral blood HCV RNA levels; Positive for HIV antibody; Positive for syphilis;
7. Symptomatic heart failure or significant arrhythmias: NYHA Class III or IV congestive heart failure; Myocardial infarction or coronary artery bypass grafting (CABG) or coronary stent implantation within ≤6 months prior to signing ICF; Clinically significant ventricular arrhythmias or unexplained syncope (except when caused by vasovagal or dehydration); Significant non-ischemic cardiomyopathy history;
8. Other significant diseases: Primary immunodeficiency; Stroke or seizure within 6 months prior to screening; Obvious clinical evidence of dementia or altered mental status; History of Parkinson's disease or Parkinsonism;
9. Surgery within 2 weeks prior to treatment or planned surgery within 2 weeks post-treatment, except for local anesthesia procedures;
10. Use of live-attenuated vaccines within 1 month before treatment;
11. Known severe allergic reaction to ESO-T01 or its formulation components;
12. Known severe allergic reaction to Tocilizumab;
13. Inability to establish venous access;
14. Any other condition deemed by the investigator as unsuitable for participation in the study.

Where this trial is running

Wuhan, Hubei

• Tongji Hospital, Tongji Medical College — Wuhan, Hubei, China (Recruiting)

Study contacts

• Study coordinator: Chunrui Li

Conditions Relapsed/ Refractory Multiple Myeloma; ESO-T01; Multiple Myeloma; in vivo