Clinical trial NCT04812691: CD19-targeted CAR T Cells （JWCAR029） for Primary Refractory Diffuse Large B Cell Lymphoma
Official title: CD19-targeted CAR T Cells （JWCAR029） for Primary Refractory Diffuse Large B Cell Lymphoma, Phase Ⅰ,Open-label,Single-arm,Muticenter Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diffuse Large B Cell Lymphoma
Keywords: Primary refractory
Lead sponsor: Shanghai Ming Ju Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-03-24
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Types, frequency, and severity of adverse events and laboratory anomalies
timeFrame: 2 years
Secondary outcomes:
measure: Complete response rate (CRR) in primary refractory DLBCL subjects
timeFrame: 1 month
measure: Objective response rate (ORR) in primary refractory DLBCL subjects
timeFrame: 1 month
measure: Best objective response rate (BORR)
timeFrame: 2 years
measure: Investigator evaluated CRR
timeFrame: 3 months
measure: Investigator evaluated ORR (ORR=CR+PR)
timeFrame: 3 months
measure: Duration of response (DOR)
timeFrame: up to 24 months after JWCAR029 infusion
measure: Duration of complete remission (DoCR)
timeFrame: up to 24 months after JWCAR029 infusion
measure: Time to response (TTR)
timeFrame: up to 24 months after JWCAR029 infusion
measure: Time to complete response (TTCR)
timeFrame: up to 24 months after JWCAR029 infusion
measure: Pharmacokinetic (PK)- Cmax of JWCAR029
timeFrame: up to 1 year after JWCAR029 infusion
measure: Pharmacokinetic (PK)- Tmax of JWCAR029
timeFrame: up to 1 year after JWCAR029 infusion
measure: Pharmacokinetic (PK)- AUC of JWCAR029
timeFrame: up to 1 year after JWCAR029 infusion
measure: Progression-free survival (PFS)
timeFrame: up to 2 year after JWCAR029 infusion
measure: Overall survival (OS)
timeFrame: up to 2 year after JWCAR029 infusion
measure: Changes of CRP and serum ferritin
timeFrame: 1 year after JWCAR029 infusion
measure: Anti-therapeutic JWCAR029 antibody
timeFrame: up to 2 year after JWCAR029 infusion
measure: The concentration of Car-T cell
timeFrame: up to 2 year after JWCAR029 infusion
measure: The proportion of Car-T cell subgroups
timeFrame: up to 2 year after JWCAR029 infusion
measure: The concentration of CD19 in tumor biopsy samples
timeFrame: up to 2 year after JWCAR029 infusion
measure: The change of serum cytokines concentration
timeFrame: up to 2 year after JWCAR029 infusion
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin hospital
state: Shanghai
city: Hangzhou
country: China
facility: Zhejiang university school of medicine first affiliated hospital
state: Zhejiang
Study officials:
affiliation: Ruijin Hospital
name: Weili Zhao
role: PRINCIPAL_INVESTIGATOR
References: