Treatment of relapsed and refractory B-cell lymphoma using CD19-targeted therapies

Exploratory Clinical Study of CD19-targeted CAR-T and CAR-DC in the Treatment of Relapsed and Refractory B-cell Lymphoma

This study is testing a new type of treatment using CD19-targeted therapies for people with relapsed and hard-to-treat B-cell lymphoma to see how safe and effective it is.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University (Academic / other)
• Drugs / interventions: rituximab, ibrutinib, CAR T, chemotherapy, radiation, CAR-T
• Locations: 1 site (Hanzhou, Zhejiang)
• Trial ID: NCT05585996 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm, dose-escalation clinical trial aims to evaluate the safety and preliminary efficacy of CD19-targeted CAR-T and CAR-DC therapies in patients with relapsed and refractory B-cell lymphoma. The study plans to enroll 6-18 patients initially, with doses determined based on a 3+3 dose-escalation principle. Primary endpoints include dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), while secondary endpoints focus on overall response rates, overall survival, and progression-free survival. Following the initial phase, an additional 52 patients will be enrolled to further assess safety and efficacy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with histologically confirmed CD19+ relapsed or refractory B-cell lymphoma who have undergone multiple lines of prior therapy.

Not a fit: Patients with non-CD19+ B-cell lymphomas or those who have not received prior chemotherapy 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 B-cell lymphomas.

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

Eligibility criteria

Inclusion Criteria:

1. Male or female participants aged 18 to 75 years old at the time enrollment, with ECOG Score of ≤ 3;
2. Patients should provide a written informed consent;
3. Histologically confirmed CD19+ DLBCL, HGBL-DHL, MCL, tFL, PMBL;

   * Confirmation obtained from central pathology review before enrollment;
   * Sufficient formalin-fixed, paraffin-embedded tumor samples were required for histologically confirmed diagnosis and detection of CD19 expression;
   * Relapsed DLBCL and tFL after ≥2 lines of chemotherapy that include rituximab and anthracycline, or refractory disease as defined in the SCHOLAR-1 study: progressive disease after receiving ≥ 4 cycles of first-line therapy or stable disease (received 2 cycles of later-line therapy) as best response to chemotherapy or relapse ≤ 12 months after autologous stem cell transplantation (ASCT);
   * Relapsed/refractory MCL after ≥ 2 lines of prior therapy, including immunochemotheapy and BTK inhibitor such as ibrutinib, or patient did not agree to receive BTK inhibitor treatment;
   * At least one measurable tumor according to revised International Working Group (IWG) Response criteria;
4. Life expectancy ≥ 3 months;
5. Adequate cardiac, pulmonary, liver, renal, and bone marrow functions, with the following laboratory values: an absolute neutrophil count \> 1,000/mm3, platelets count ≥ 45,000/mm3, and hemoglobin \> 8.0g/dl; alanine aminotransferase and aspartate aminotransferase ≤ 2.5 × the upper limit of the normal range (ULN), and total bilirubin ≤ 2.0 mg/dl; a serum creatinine of ≤ 1.5 × ULN; a left ventricular ejection fraction ≥ 50%;

Exclusion Criteria:

1. Prior treatment that included anti-CD19-targeted therapy, CAR T cell therapy, gene therapy, and allogenic hematopoietic stem cell transplantation (allo-HSCT);
2. Chemotherapy other than lymphodepleting chemotherapy, therapeutic doses of steroids, immunosuppressive agent, any radiation therapy or anti-tumor targeted therapy including lenalidomide, bortezomib, ibrutinib, received within 2 weeks before cell collection;
3. Clinical trial with investigational drug was performed within 4 weeks;
4. History of other cancers;
5. Active hepatitis B or hepatitis C. Hepatitis B: HBV-DNA ≥ 1,000 IU/ml; Hepatitis C: HCV RNA positive;
6. HIV infection;
7. Uncontrollable infection of active bacteria and fungi;
8. Currently pregnant or refusal to practice birth control within 1 year;
9. Active autoimmune or inflammatory diseases;
10. Central nervous system lymphoma.

Where this trial is running

Hanzhou, Zhejiang

• 2nd Affiliated Hospital, School of Medicine, Zhejiang University — Hanzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Wenbin Qian, MD, PhD — 2nd Affiliated Hospital, School of Medicine, Zhejiang Universit
• Study coordinator: Wenbin Qian, PhD

Conditions Relapsed and Refractory B-cell Lymphoma