Using CAR-T therapy to treat relapsed or refractory non-Hodgkin lymphoma

This is a Phase I Clinical Study to Evaluate the Safety and Efficacy of CAR-T Infusion Preparation in the Treatment of CD19-positive Relapsed/Refractory Non-Hodgkin Lymphoma.

This study is testing a new CAR-T cell therapy to see if it can safely help people with relapsed or hard-to-treat non-Hodgkin lymphoma.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chongqing Precision Biotech Co., Ltd (Industry-sponsored)
• Drugs / interventions: ipilimumab, nivolumab, pembrolizumab, atezolizumab, CAR-T, CAR T, chemotherapy, cyclophosphamide, fludarabine
• Locations: 1 site (Jinan, Shandong)
• Trial ID: NCT05420493 on ClinicalTrials.gov

What this trial studies

This phase I clinical study evaluates the safety and efficacy of CAR-T cell therapy specifically for patients with CD19-positive relapsed or refractory non-Hodgkin lymphoma. Participants will undergo leukapheresis to collect their own lymphocytes, which will then be modified to create CAR-T cells. Following the cell preparation, patients will receive lymphodepleting chemotherapy before the infusion of the CAR-T cells at a targeted dose. The study aims to determine how well this treatment works and its safety profile.

Who should consider this trial

Good fit: Ideal candidates are patients with CD19-positive non-Hodgkin lymphoma who have relapsed or are refractory after previous treatments.

Not a fit: Patients with non-CD19-positive non-Hodgkin lymphoma or those who have not received prior treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat non-Hodgkin lymphoma.

How similar studies have performed: Other studies using CAR-T therapy for similar conditions have shown promising results, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. CD19-positive non-Hodgkin lymphoma confirmed by cytology or histology according to WHO2016 criteria:

   1. Diffuse large B-cell lymphoma: including unspecified (DLBCL, NOS), chronic inflammation-related DLBCL, primary cutaneous DLBCL (leg type), EBV-positive DLBCL (NOS); and high-grade B-cell lymphoma (including high-grade B-cell lymphoma, NOS, and high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements); and primary mediastinal large B-cell lymphoma; and T-cell-rich histiocytosis B-cell lymphoma; and transformed DLBCL (such as follicular lymphoma, chronic lymphocytic leukemia/small B-lymphocytic lymphoma transformed DLBCL); patients with the above tumor types have been treated with at least first- and second-line drugs and have stable disease for ≤12 months , or when the best Disease progression after efficacy; or disease progression or relapse after autologous stem cell transplantation ≤12 months;
   2. According to WHO2016 criteria cytology or histology confirmed CD19 positive: follicular cell lymphoma. Patients with this tumor type have received at least third-line therapy, and recurrence or disease progression has occurred within 2 years after third-line therapy or more. Currently in disease progression, stable disease, or partial remission;
   3. According to WHO2016 standard cytology or histology confirmed CD19 positive: mantle cell lymphoma. Such patients have not been cured or relapsed after at least three-line treatment and are not suitable for stem cell transplantation or relapse after stem cell transplantation;
2. Age ≥18 years old (including the threshold);
3. According to the 2014 version of Lugano criteria, there is at least one two-dimensional measurable lesion as the evaluation basis: for intranodal lesions, it is defined as: long diameter \>1.5cm; for extranodal lesions, long diameter should be \>1.0cm;
4. Eastern Cooperative Oncology Group activity status score ECOG score 0-2;
5. The venous access required for collection can be established, and there are enough cells collected by non-mobilized apheresis for CAR-T cell production;
6. Liver and kidney function, cardiopulmonary function meet the following requirements:

   * Serum creatinine≤2.0×ULN;
   * Left ventricular ejection fraction ≥ 50% and no obvious pericardial effusion, no abnormal ECG;
   * Blood oxygen saturation ≥92% in non-oxygen state;
   * Blood total bilirubin≤2.0×ULN (except without clinical significance);
   * ALT and AST≤3.0×ULN (with liver tumor infiltration≤5.0×ULN);
7. Be able to understand and voluntarily sign the informed consent.

Exclusion Criteria:

1. Received CAR-T therapy or other gene-modified cell therapy before screening;
2. Received anti-tumor therapy (except systemic immune checkpoint inhibition or stimulation therapy) within 2 weeks or 5 half-lives (whichever is shorter) before screening. 3 half-lives are required to enroll (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 receptor agonist, 4-1BB receptor agonist, etc.);
3. Those who have received hematopoietic stem cell transplantation (ASCT) within 12 weeks before apheresis, or who have previously received allogeneic hematopoietic stem cell transplantation (HSCT), or those who have solid organ transplantation; immunosuppression is required within 2 weeks before apheresis Grade 2 and above GVHD of the drug;
4. Patients with atrial or ventricular lymphoma involvement or need urgent treatment due to tumor mass such as intestinal obstruction or vascular compression;
5. Have been vaccinated with live attenuated vaccine within 6 weeks before clearing the leprosy;
6. Cerebrovascular accident or epilepsy occurred within 6 months before signing the ICF;
7. History of myocardial infarction, cardiac bypass or stent, unstable angina or other clinically significant heart disease within 12 months prior to signing the ICF;
8. Active or uncontrolled autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), except those that do not require systemic treatment;
9. Malignant tumors other than non-Hodgkin lymphoma within 5 years prior to screening, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, Ductal carcinoma in situ;
10. Uncontrollable infection within 1 week before screening;
11. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is greater than the normal reference range; or hepatitis C virus (HCV) antibody positive and peripheral blood C Hepatitis virus (HCV) RNA titer test is greater than the normal reference range; or human immunodeficiency virus (HIV) antibody positive; or syphilis test positive; cytomegalovirus (CMV) DNA test positive;
12. Women who are pregnant or breastfeeding; or women of childbearing age who have a positive pregnancy test during the screening period; or male or female patients who are unwilling to use contraception from the time of signing the informed consent form to 1 year after receiving CAR-T cell infusion;
13. Other investigators deem it inappropriate to participate in the study.

Where this trial is running

Jinan, Shandong

• Shandong Second Provincial General Hospital — Jinan, Shandong, China (Recruiting)

Study contacts

• Principal investigator: Jianfeng Bi, M.D — Shandong Second Provincial General Hospital
• Study coordinator: Jingwang Bi, M.D

Conditions Relapsed Non-Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Non Hodgkin Lymphoma; CAR-T