Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Lymphoma, Non-Hodgkin
Conditions
Keywords
JWCAR029, B-Cell Malignancies, non-Hodgkin lymphoma, CAR T cells, Chimeric antigen receptor, Relapsed/Refractory
Brief summary
This is a phase II, open-label, single-arm, multicenter study to asess the efficacy and safety of JWCAR029 in adult R/R Non-Hodgkins Lymphoma subjects in China.
Detailed description
This is a phase II, open-label, single-arm, multicenter study conducted in adult subjects with R/R Non-Hodgkins Lymphoma in China to evaluate the safety, efficacy, pharmacokinetics(PK), pharmacodynamics(PD) of JWCAR029 and collect the patient reported quality of life changes and immune response after JWCAR029 treatment. There will be two cohorts of cohort A and cohort B. Large B cell lymphoma (LBCL) patients will be enrolled in cohort A and follicular lymphoma patients will be enrolled in cohort B. Two dose levels of 1.0 x 10\^8 CAR+ T cells and 1.5 x 10\^8 CAR+ T cells are adopted in this study in both cohorts, subjects will be randomly assigned into the two dose levels with a 1:1 ratio. All sujects will be followed for 2 years following JWCAR029 infusion.
Interventions
JWCAR029 be administered at dose level: 1 x 10\^8 CAR+T cells and 1.5 x 10\^8 CAR+T cells
Sponsors
Shanghai Ming Ju Biotechnology Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects must meet all of the following criteria to participate in the study: 1. ≥ 18 years old; 2. Sign on the informed consent; 3. Subject must have histologically confirmed large B lymphoma or follicular lymphoma; 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. Central nervous system (CNS) only involvement by malignancy or primary CNS lymphoma; 2. History of another primary malignancy that has not been in remission for at least 2 years; 3. Subjects has HBV, HCV, HIV or syphilis infection at the time of screening; 4. Deep venous thrombosis (DVT)/Pulmonary embolism (PE), or DVT/PE requires anti-coagulation within 3 months prior to signing the ICF; 5. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection; 6. Presence of acute or chronic graft-versus-host disease (GVHD); 7. History of any serious cardiovascular disease or presence of clinically relevant CNS pathology; 8. Pregnant or nursing women; 9. 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; 10. Uncontrolled conditions or unwillingness or inability to follow the procedures required in the protocol; 11. Received CAR T-cell or other genetically-modified T-cell therapy previously.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) in LBCL subjects in cohort A; | 3 months | Objective response rate (ORR) in 3 month in cohort A of large B cell lymphoma (LBCL) subjects； |
| Complete response rate (CRR) in FL subjects in cohort B | 3 months | Complete response rate (CRR) in 3 month in cohort B of follicular lymphoma (FL) subjects |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events (AEs) | up to 24 months after JWCAR029 infusion | Number of participants with adverse events, type of adverse events, severity of adverse events, and number of participants with laboratory abnormalities, type of laboratory abnormalities and severity of laboratory abnormalities. |
| Duration of response (DOR) | up to 24 months after JWCAR029 infusion | Time from first response(PR or CR) to disease progression or death from any cause. |
| Duration of complete remission (DoCR) | up to 24 months after JWCAR029 infusion | Time from complete response (CR) to disease progression or death from any cause. |
| Duration of partial remission (DoPR) | up to 24 months after JWCAR029 infusion | Time from partial response (PR) to disease progression or death from any cause. |
| Time to response (TTR) | up to 24 months after JWCAR029 infusion | Time from JWCAR029 infusion to first documentation of CR or PR |
| Time to complete response (TTCR) | up to 24 months after JWCAR029 infusion | Time from JWCAR029 infusion to first documentation of CR |
| Pharmacokinetic (PK)- Cmax of JWCAR029 | up to 1 year after JWCAR029 infusion | Maximum observed concentration of JWCAR029 in peripheral blood |
| Pharmacokinetic (PK)- Tmax of JWCAR029 | up to 1 year after JWCAR029 infusion | Time to maximum concentration of JWCAR029 in the peripheral blood |
| Pharmacokinetic (PK)- AUC of JWCAR029 | up to 1 year after JWCAR029 infusion | Area under the concentration vs time curve of JWCAR029 |
| Progression-free survival (PFS) | 3 to 5 years after JWCAR029 infusion | — |
| Complete response rate (CRR) in cohort A of LBCL subjects | 3 months | — |
| Quality of Life C30 questionnaire (EORTC-QLQ-C30) | up to 2 year after JWCAR029 infusion | EORTC-QLQ-C30 is composed of both multi-item scales and single item measures. These include five functional scales (physical, role, emotional, cognitive and social), three symptom scales (fatigue, nausea/vomiting, and pain), a global health status/health-related quality of life (HRQoL) scale, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Each of the multi-item scales includes a different set of items - no item occurs in more than one scale |
| European Quality of Life-5 Dimensions health state classifier to 5 Levels (EQ-5D-5L) | up to 2 year after JWCAR029 infusion | The EQ-5D-5L consists of the EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, extreme problems) |
| ICU and non-ICU hospitalization days | up to 2 year after JWCAR029 infusion | — |
| ICU and non-ICU hospitalization reasons | up to 2 year after JWCAR029 infusion | — |
| Anti-therapeutic JWCAR029 antibody | up to 2 year after JWCAR029 infusion | — |
| Changes of T cell counts, subgroups and serum cytokines | up to 2 year after JWCAR029 infusion | — |
| CD19 expression in tumor biopsy samples | up to 2 year after JWCAR029 infusion | — |
| Changes of inflammation biomarkers-CRP | up to 1 year after JWCAR029 infusion | — |
| Changes of inflammation biomarkers-serum ferritin | up to 1 year after JWCAR029 infusion | — |
| Overall survival | 3 to 5 years after JWCAR029 infusion | — |
| Objective response rate (ORR) in cohort B of FL subjects | 3 months | — |
Countries
China
Outcome results
None listed