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

Zhejiang University

Status and phase: Enrolling; Phase 1

Conditions: Relapsed and Refractory B-cell Lymphoma

Treatments: Biological: CD19 CAR-T and CD19 CAR-DC

Study type: Interventional

Funder types: Other

Identifiers

NCT05585996

2022-0160

Details and patient eligibility

About

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

Full 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.

Enrollment: 70 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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70 participants in 1 patient group

Combination therapy of CD19 CAR-T and CD19 CAR-DC

Experimental group

Description:

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.

Treatment:

Biological: CD19 CAR-T and CD19 CAR-DC