Diffuse Large B Cell Lymphoma
Conditions
Keywords
Primary refractory
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.
Interventions
BIOLOGICALJWCAR029 (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.
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
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Types, frequency, and severity of adverse events and laboratory anomalies | 2 years | Physiological parameter |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) in primary refractory DLBCL subjects | 1 month | Investigator evaluated ORR in 1 month |
| Best objective response rate (BORR) | 2 years | The best response from the onset of treatment to the onset of disease progression/recurrence or to the onset of another anticancer treatment |
| Investigator evaluated CRR | 3 months | Complete response rate (CRR) |
| Investigator evaluated ORR (ORR=CR+PR) | 3 months | Complete response (CR) + partial response（PR） |
| 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 |
| 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 |
| Complete response rate (CRR) in primary refractory DLBCL subjects | 1 month | Investigator evaluated CRR in 1 month |
| 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) | up to 2 year after JWCAR029 infusion | Progression-free survival |
| Overall survival (OS) | up to 2 year after JWCAR029 infusion | Overall survival |
| Changes of CRP and serum ferritin | 1 year after JWCAR029 infusion | Changes of inflammation biomarkers-CRP and serum ferritin |
| Anti-therapeutic JWCAR029 antibody | up to 2 year after JWCAR029 infusion | The level of anti-therapeutic JWCAR029 antibody after JWCAR029 infusion |
| The concentration of Car-T cell | up to 2 year after JWCAR029 infusion | The concentration of Car-T cells |
| The proportion of Car-T cell subgroups | up to 2 year after JWCAR029 infusion | The proportion of Car-T cell subgroups after infusion |
| The concentration of CD19 in tumor biopsy samples | up to 2 year after JWCAR029 infusion | The concentration of CD19 in tumor biopsy samples |
| The change of serum cytokines concentration | up to 2 year after JWCAR029 infusion | The change of serum cytokines concentration after JWCAR029 infusion |
| Pharmacokinetic (PK)- Tmax of JWCAR029 | up to 1 year after JWCAR029 infusion | Time to maximum concentration of JWCAR029 in the peripheral blood |
Countries
China
Outcome results
None listed