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

Diffuse Large B Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04812691
• Other study ID #: JWCAR029-003
• Status: Completed
• Phase: Phase 1
• Start date: July 10, 2020
• Est. completion date: April 25, 2023

Study information

• Verified date: November 2023
• Source: Shanghai Ming Ju Biotechnology Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 25, 2023
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

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.

Locations

Country	Name	City	State
China	Zhejiang university school of medicine first affiliated hospital	Hangzhou	Zhejiang
China	Ruijin hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Ming Ju Biotechnology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Types, frequency, and severity of adverse events and laboratory anomalies	Physiological parameter	2 years
Secondary	Complete response rate (CRR) in primary refractory DLBCL subjects	Investigator evaluated CRR in 1 month	1 month
Secondary	Objective response rate (ORR) in primary refractory DLBCL subjects	Investigator evaluated ORR in 1 month	1 month
Secondary	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
Secondary	Investigator evaluated CRR	Complete response rate (CRR)	3 months
Secondary	Investigator evaluated ORR (ORR=CR+PR)	Complete response (CR) + partial response(PR)	3 months
Secondary	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
Secondary	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
Secondary	Time to response (TTR)	Time from JWCAR029 infusion to first documentation of CR or PR	up to 24 months after JWCAR029 infusion
Secondary	Time to complete response (TTCR)	Time from JWCAR029 infusion to first documentation of CR	up to 24 months after JWCAR029 infusion
Secondary	Pharmacokinetic (PK)- Cmax of JWCAR029	Maximum observed concentration of JWCAR029 in peripheral blood	up to 1 year after JWCAR029 infusion
Secondary	Pharmacokinetic (PK)- Tmax of JWCAR029	Time to maximum concentration of JWCAR029 in the peripheral blood	up to 1 year after JWCAR029 infusion
Secondary	Pharmacokinetic (PK)- AUC of JWCAR029	Area under the concentration vs time curve of JWCAR029	up to 1 year after JWCAR029 infusion
Secondary	Progression-free survival (PFS)	Progression-free survival	up to 2 year after JWCAR029 infusion
Secondary	Overall survival (OS)	Overall survival	up to 2 year after JWCAR029 infusion
Secondary	Changes of CRP and serum ferritin	Changes of inflammation biomarkers-CRP and serum ferritin	1 year after JWCAR029 infusion
Secondary	Anti-therapeutic JWCAR029 antibody	The level of anti-therapeutic JWCAR029 antibody after JWCAR029 infusion	up to 2 year after JWCAR029 infusion
Secondary	The concentration of Car-T cell	The concentration of Car-T cells	up to 2 year after JWCAR029 infusion
Secondary	The proportion of Car-T cell subgroups	The proportion of Car-T cell subgroups after infusion	up to 2 year after JWCAR029 infusion
Secondary	The concentration of CD19 in tumor biopsy samples	The concentration of CD19 in tumor biopsy samples	up to 2 year after JWCAR029 infusion
Secondary	The change of serum cytokines concentration	The change of serum cytokines concentration after JWCAR029 infusion	up to 2 year after JWCAR029 infusion