CD19-targeted CAR T Cells （JWCAR029） for Primary Refractory Diffuse Large B Cell Lymphoma

CD19-targeted CAR T Cells （JWCAR029） for Primary Refractory Diffuse Large B Cell Lymphoma, Phase Ⅰ,Open-label,Single-arm,Muticenter Study

This is a phase I, open-label, single-arm, multicenter study to assess the safety and efficacy of JWCAR029 in adult primary refractory DLBCL subjects in China

Study Overview

• Status: Completed
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Biological: JWCAR029 (CD19-targeted Chimeric Antigen Receptor Cells)

Detailed Description

This is a phase I, open-label, single-arm, multicenter study conducted in adult subjects with primary refractory DLBCL in China to evaluate the safety, efficacy, pharmacokinetics(PK), pharmacodynamics(PD) of JWCAR029 and collect immune response after JWCAR029 treatment.

One dose level of 1.0 x 10^8 CAR+ T cells is adopted in this study. All sujects will be followed for 2 years after JWCAR029 infusion.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: JWCAR029Medical Shanghai Ming Ju Biotechnology Co., Ltd; Phone Number: +86 21 50464201; Email: JWCAR029Medical@jwtherapeutics.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Ruijin Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Zhejiang university school of medicine first affiliated hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. ≥ 18 years old;
2. Sign on the informed consent;
3. Subject must have histologically confirmed diffuse large B lymphoma and primary refractory with first-line therapy;
4. Subjects have accessible PET-positive lesion and have measurable CT-positive lesion according to Lugano Classification;
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
6. Adequate organ function;
7. Adequate vascular access for leukapheresis procedure;
8. Subjects who have previously received CD19 targeted therapy must confirm that lymphoma lesions still express CD19;
9. Women of childbearing potential must agree to use highly effective methods of contraception for 1 year after the last dose of JWCAR029;
10. Males who have partners of childbearing potential must agree to use an effective barrier contraceptive method for 1 year after the last dose of JWCAR029

Exclusion Criteria:

1. Subjects who have received second-line treatment or above
2. CD19 negative
3. Primary CNS lymphoma;
4. History of another primary malignancy that has not been in remission for at least 2 years;
5. Subjects has HBV, HCV, HIV or syphilis infection at the time of screening;
6. Deep venous thrombosis (DVT)/Pulmonary embolism (PE), or DVT/PE requires anti-coagulation within 3 months prior to signing the ICF;
7. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection;
8. Presence of acute or chronic graft-versus-host disease (GVHD);
9. History of any serious cardiovascular disease or presence of clinically relevant CNS pathology;
10. Pregnant or nursing women;
11. Subjects using of any chemotherapy, corticisteriod, experiment agents, GVHD therapies, radiation, allo-HSCT or any other therapies for lymphoma must go through a specific wash-out period before leukapheresis;
12. Uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol;
13. Received CAR T-cell or other genetically-modified T-cell therapy previously.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: JWCAR029; The safety and efficacy of JWCAR029 will be evaluated in 1 x 10^8 CAR+T cells dose level

Biological: JWCAR029 (CD19-targeted Chimeric Antigen Receptor Cells); Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JWCAR029. During JWCAR029 production, subjects will receive a conditioning chemotherapy regimen of cyclophosphamide and fludarabine for the purpose of lymphocytes depletion. After lymphodepletion, subjects will receive 1 x 10^8 CAR+T cells (JWCAR029) treatment by intravenous (IV) injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Types, frequency, and severity of adverse events and laboratory anomalies	Physiological parameter	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate (CRR) in primary refractory DLBCL subjects	Investigator evaluated CRR in 1 month	1 month
Objective response rate (ORR) in primary refractory DLBCL subjects	Investigator evaluated ORR in 1 month	1 month
Best objective response rate (BORR)	The best response from the onset of treatment to the onset of disease progression/recurrence or to the onset of another anticancer treatment	2 years
Investigator evaluated CRR	Complete response rate (CRR)	3 months
Investigator evaluated ORR (ORR=CR+PR)	Complete response (CR) + partial response（PR）	3 months
Duration of response (DOR)	Time from first response(PR or CR) to disease progression or death from any cause	up to 24 months after JWCAR029 infusion
Duration of complete remission (DoCR)	Time from complete response (CR) to disease progression or death from any cause	up to 24 months after JWCAR029 infusion
Time to response (TTR)	Time from JWCAR029 infusion to first documentation of CR or PR	up to 24 months after JWCAR029 infusion
Time to complete response (TTCR)	Time from JWCAR029 infusion to first documentation of CR	up to 24 months after JWCAR029 infusion
Pharmacokinetic (PK)- Cmax of JWCAR029	Maximum observed concentration of JWCAR029 in peripheral blood	up to 1 year after JWCAR029 infusion
Pharmacokinetic (PK)- Tmax of JWCAR029	Time to maximum concentration of JWCAR029 in the peripheral blood	up to 1 year after JWCAR029 infusion
Pharmacokinetic (PK)- AUC of JWCAR029	Area under the concentration vs time curve of JWCAR029	up to 1 year after JWCAR029 infusion
Progression-free survival (PFS)	Progression-free survival	up to 2 year after JWCAR029 infusion
Overall survival (OS)	Overall survival	up to 2 year after JWCAR029 infusion
Changes of CRP and serum ferritin	Changes of inflammation biomarkers-CRP and serum ferritin	1 year after JWCAR029 infusion
Anti-therapeutic JWCAR029 antibody	The level of anti-therapeutic JWCAR029 antibody after JWCAR029 infusion	up to 2 year after JWCAR029 infusion
The concentration of Car-T cell	The concentration of Car-T cells	up to 2 year after JWCAR029 infusion
The proportion of Car-T cell subgroups	The proportion of Car-T cell subgroups after infusion	up to 2 year after JWCAR029 infusion
The concentration of CD19 in tumor biopsy samples	The concentration of CD19 in tumor biopsy samples	up to 2 year after JWCAR029 infusion
The change of serum cytokines concentration	The change of serum cytokines concentration after JWCAR029 infusion	up to 2 year after JWCAR029 infusion

Collaborators and Investigators

• Sponsor: Shanghai Ming Ju Biotechnology Co., Ltd.
• Investigators: Principal Investigator: Weili Zhao, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2020
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): April 25, 2023

Study Registration Dates

• First Submitted: January 18, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Estimated): November 22, 2023
• Last Update Submitted That Met QC Criteria: November 21, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Primary refractory
• 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; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: JWCAR029-003

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
• product manufactured in and exported from the U.S.: No