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

Phase 1

Recruiting

• Conditions: Relapsed and Refractory B-cell Lymphoma
• Interventions: Biological: CD19 CAR-T and CD19 CAR-DC

• Registration Number: NCT05585996
• Lead Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University

Brief Summary

This is an open, single-arm, prospective, dose-escalation clinical trial designed to evaluate the safety and the preliminary efficacy of CD19-targeted CAR-T combined with CAR-DC in the treatment of relapsed and refractory B-cell lymphoma

Detailed Description

6-18 patients are planned to be enrolled in the dose-escalation trial. The dose of CD19-CAR-DC was according to the 3+3 dose-escalation principle (0.25×10\^6/kg, 0.5×10\^6/kg, 0.75×10\^6/kg ( ±20%) . CAR-T was 2×10\^6/kg . The primary endpoints are DLT, MTD, and the second endpionts are the overall response rates (CR and PR), overall survival, and progression-free survival. Based on the results in the dose-escalation trial, the recommended dose will be determined. Another 52 patients will be enrolled to continue estimating the safety and efficacy.

Study Timeline

• Study Start: 2022-08-01
• Study First Submitted: 2022-10-16
• Study First Submitted QC: 2022-10-16
• Study First Posted: 2022-10-19
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-02
• Last Update Posted: 2023-02-06
• Primary Completion: 2025-11-01
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Combination therapy of CD19 CAR-T and CD19 CAR-DC	CD19 CAR-T and CD19 CAR-DC	6-18 patientsare planned to be enrolled in the dose-escalation trial (0.5×10\^6/kg、1×10\^6/kg、2×10\^6/kg和4×10\^6/kg) and 52 patients in the dose-expansion trial.

Primary Outcome Measures

Name	Time	Method
MTD	Up to 28 days	MTD was the highest dose for DLT in ≤1/6 subjects
Incidence of abnormalities	Up to 28 days	Incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.
DLT	Up to 28 days	To evaluate the safety, tolerability, and determine the recommended dosage of combined therapy of CD19 CAR-T and CD19 CAR-DC for Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate	Up to 2 years	The proportion of CR or PR patients as assessed by investigators based on Lugano 2014 Response Assessment
Duration of Response	Up to 2 years	The time from the start of the first assessment of CR or PR to the first assessment as disease recurrence or progression or death
Progression Free Survival	Up to 2 years	The length of time that a participant's disease did not progress during or after CAR-T treatment.

Trial Locations

Locations (1)

2nd Affiliated Hospital, School of Medicine, Zhejiang University; 🇨🇳 Hanzhou, Zhejiang, China