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

NCT ID: NCT05585996

Last Updated: 2023-02-06

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-01
• Study Completion Date: 2025-12-30

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.

Conditions

Relapsed and Refractory B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Combination therapy of 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.

Group Type: EXPERIMENTAL

CD19 CAR-T and CD19 CAR-DC

Intervention Type: BIOLOGICAL

Intravenously injected CAR DC cells and followed by CAR T cells 4 hours later

Interventions

CD19 CAR-T and CD19 CAR-DC

Intravenously injected CAR DC cells and followed by CAR T cells 4 hours later

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wenbin Qian, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

2nd Affiliated Hospital, School of Medicine, Zhejiang Universit

Locations

2nd Affiliated Hospital, School of Medicine, Zhejiang University

Hanzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wenbin Qian, PhD

Role: CONTACT

qianwb@zju.edu.cn

13605801032

Wen Lei, PhD

Role: CONTACT

leiwen2017@zju.edu.cn

18258448016

Facility Contacts

Wenbin Qian, PhD

Role: primary

qianwb@zju.edu.cn

+8613605801032

Hui Liu, PhD

Role: backup

sylen@zju.edu.cn

13819198629

Other Identifiers

2022-0160

Identifier Type: -

Identifier Source: org_study_id