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

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

Study Overview

• Status: Recruiting
• Conditions: Relapsed and Refractory B-cell Lymphoma
• Intervention / Treatment: Biological: CD19 CAR-T and CD19 CAR-DC

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 Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wenbin Qian, PhD; Phone Number: 13605801032; Email: qianwb@zju.edu.cn
• Study Contact Backup: Name: Wen Lei, PhD; Phone Number: 18258448016; Email: leiwen2017@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hanzhou, Zhejiang, China, 310009
      • Recruiting
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Biological: CD19 CAR-T and CD19 CAR-DC; Intravenously injected CAR DC cells and followed by CAR T cells 4 hours later

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD	MTD was the highest dose for DLT in ≤1/6 subjects	Up to 28 days
Incidence of abnormalities	Incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.	Up to 28 days
DLT	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	Up to 28 days

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Principal Investigator: Wenbin Qian, MD, PhD, 2nd Affiliated Hospital, School of Medicine, Zhejiang Universit

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2022
• Primary Completion (ANTICIPATED): November 1, 2025
• Study Completion (ANTICIPATED): December 30, 2025

Study Registration Dates

• First Submitted: October 16, 2022
• First Submitted That Met QC Criteria: October 16, 2022
• First Posted (ACTUAL): October 19, 2022

Study Record Updates

• Last Update Posted (ACTUAL): February 6, 2023
• Last Update Submitted That Met QC Criteria: February 2, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell
• Other Study ID Numbers: 2022-0160

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No