Treatment for B-cell lymphoma that relapsed after CAR T-cell therapy

A Single-center, Dose Selection Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Allogeneic CAR-T Targeting CD19 in Patients With Auto-CAR T Relapsed B-cell Non-Hodgkin's Lymphoma

This study is testing a new CAR-T therapy called ThisCART19A to see if it can help people with B-cell lymphoma that came back after their previous CAR-T treatment.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The First Affiliated Hospital of Soochow University (Academic / other)
• Drugs / interventions: CAR T, CAR-T, chemotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Suzhou, Jiangsu)
• Trial ID: NCT05691153 on ClinicalTrials.gov

What this trial studies

This phase 1, single-center study evaluates the efficacy, safety, and pharmacokinetics of ThisCART19A, an allogeneic CAR-T therapy targeting CD19, in patients with B-cell non-Hodgkin's lymphoma that has relapsed after auto-CAR T therapy. Participants will undergo lymphodepletion chemotherapy before receiving an intravenous infusion of ThisCART19A. The study aims to identify the most effective treatment regimen while ensuring a favorable safety profile, with follow-up lasting up to two years.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with relapsed B-cell non-Hodgkin's lymphoma after auto-CAR T therapy and a life expectancy of at least 12 weeks.

Not a fit: Patients with other types of lymphoma or those who do not meet the eligibility criteria, such as inadequate organ function or performance status, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with relapsed B-cell non-Hodgkin's lymphoma after previous CAR T-cell therapy.

How similar studies have performed: Other studies have explored CAR-T therapies for B-cell lymphomas, showing promising results, but the specific approach of ThisCART19A is novel.

Eligibility criteria

Inclusion Criteria:

1. Voluntarily sign a documented IRB-approved ICF prior to any screening procedure;
2. Gender not restricted, 18 years ≤ age ≤ 75 years;
3. Subjects with Auto-CAR T relapsed B-cell non-Hodgkin's lymphoma;
4. Life expectancy ≥ 12 weeks at the time of enrollment;
5. Eastern Cooperative Oncology Group performance status score of 0 or 1;
6. At least one measurable lesion to be assessed, with any nodal lesion \> 15mm in LDi (longest diameter) and any extranodal lesion \> 10mm in LDi;
7. Subject has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as:

   1. Adequate marrow function for lymphodepletion chemotherapy: 14 days before enrollment, absolute neutrophil count (ANC) ≥ 1×10\^9/L, platelet count ≥ 30×10\^9/L, hemoglobin ≥ 80 g/L without blood transfusion;
   2. Creatinine clearance ≥ 30 ml/min according to the Cockcroft-Gault formula, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × the upper limit of normal (ULN), total bilirubin ≤ 2×ULN (Subjects with Gilbert syndrome or liver involvement may be enrolled if their total bilirubin is ≤ 3×ULN);
   3. Pulmonary function: Baseline oxygen saturation (SaO2) ≥ 92% on room air;
   4. Cardiac function：left ventricular ejection fraction (LVEF) ≥ 40% assessed by echocardiography.
8. CD19-positive lymphoma confirmed on a biopsy during screening.

Exclusion Criteria:

1. Allergic to preconditioning measures in the trial.
2. Other malignancies apart from B-cell malignancies within 5 years prior to screening. (Subjects with cured skin squamous carcinoma, basal carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be recruited.)
3. Severe active infection (Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted).
4. Pulmonary embolism (PE) within 3 months prior to enrollment.
5. Intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases assessed by the investigator prior to enrollment.
6. Gastrointestinal involvement at risk of active bleeding.
7. Massive pericardial effusion, symptomatic thoracic or abdominal effusion.
8. Presence of CNS involvement (both primary and secondary) at screening confirmed by imaging or CSF testing.
9. Active hepatitis B virus (serum HBV-DNA ≥ 2000 IU/mL), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or active syphilis infection prior to enrollment. (Patients with HBV-DNA \< 2000 IU/mL can be enrolled, but should be administered antiviral drugs such as entecavir and tenofovir with relative clinical indicators monitored simultaneously during the treatment.)
10. Less than 100 days after allogeneic hematopoietic stem cell transplantation.
11. Vaccinated with influenza vaccine within 2 weeks prior to lymphodepletion chemotherapy. (Patients vaccinated with SARS-COV19 vaccine or inactivated; live/non-live adjuvant vaccines can be enrolled.)
12. Under treatment for graft versus host disease (GvHD). (GvHD cured subjects who had stopped immunosuppressive drugs for at least 1 month can be enrolled.)
13. Female subjects who are pregnant, breastfeeding or planning for pregnancy within 1 year after CAR-T cell infusion, or male subjects whose partners are planning for pregnancy within 1 year after CAR-T cell infusion;
14. Any conditions that would, in the investigator's assessment, increase risks in patients or interfere with the outcomes of the trial.

Where this trial is running

Suzhou, Jiangsu

• The First Affiliated Hospital of Soochow University — Suzhou, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Jia Chen, M.D., Ph.D.

Conditions CAR; B Cell Lymphoma; Relapsed Non-Hodgkin Lymphoma; Universal CAR-T