A Single Dose-escalation Study to Evaluate the Safety, Efficacy and Pharmacokinetics of Allogeneic CAR-T Targeting CD19 in Patients With Refractory or Relapsed B Cell Lymphoma
Overview
- Phase
- Phase 1
- Intervention
- ThisCART19A
- Conditions
- Allogeneic, CAR-T, Protein Sequestration, Non-gene Edited, r/r B-NHL
- Sponsor
- Zhengzhou University
- Enrollment
- 15
- Primary Endpoint
- Dose limited toxicity(DLT) observation in patient with NHL during dose escalation stage
- Status
- Not yet recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
This is a single dose escalation study to evaluate the safety, efficacy and pharmacokinetics of ThisCART19A (Allogeneic CAR-T targeting CD19) in patients with refractory or relapsed CD19 positive B cell Lymphoma.
Detailed Description
This is a single-center, nonrandomized, open-label, dose-escalation study to evaluate the safety, efficacy and pharmacokinetics of ThisCART19A in patients with refractory or relapsed CD19 positive B cell Lymphoma, such as Diffuse large B-cell lymphoma (DLBCL) , follicular lymphoma and etc.
Investigators
Mingzhi Zhang
Principal Investigator
Zhengzhou University
Eligibility Criteria
Inclusion Criteria
- •Male or female aged ≥ 18 years old;
- •Histologically confirmed diagnosis per WHO Classification Criteria for Lymphocytic Tumors 2017, including follicular lymphoma (FL), marginal zone lymphoma (MZL, including SMZL, NMZL and extranodal MZL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), etc;
- •Relapsed or refractory B-cell NHL.
- •Adequate treatment :
- •Follicular lymphoma should be treated with at least two prior treatment including alkylating agents and anti-CD20 mAbs;
- •Marginal zone lymphoma should be treated with at least two prior treatment including anti-CD20 mAbs;
- •mantle cell lymphoma should be treated with a first-line therapy including anthracyclines/bendamoxetine+anti-CD20 mAbs;
- •Diffuse large B lymphoma, not otherwise specified (DLBCL, NOS), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double/triple hit lymphoma, DHL/THL), diffuse large B-cell lymphoma (DLBCL) transformed from follicular lymphoma (FL), histological grade 3b follicular lymphoma. relapsed or primary refractory lymphoma within 12 months after first-line treatment, first-line therapy including anthracycline and anti-CD20 mAbs.
- •Failing to autologous CAR-T therapy.
- •Estimated life expectancy \> 12 weeks deemed by investigator；
Exclusion Criteria
- •Allergic to preconditioning measures.
- •HP-positive MALT;
- •Patients with risks of deep gastrointestinal ulcers, perforation or gastrointestinal bleeding
- •Patients with other malignancies other than B-cell malignancies within 5 years prior to screening. Patients with cured skin squamous carcinoma, basal carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be recruited.
- •Uncontrollable bacterial, fungal and viral infection during screening.
- •Patients had pulmonary embolism (PE) and/or deep vein thrombosis (DVT) within 3 months prior to enrollment.
- •Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment.
- •Imaging confirmed the presence of central nervous system involvement (both primary and secondary) and obvious symptoms at the time of screening.
- •Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or Human immunodeficiency virus (HIV) or Syphilis infection. HBV-DNA \< 2000 IU/mL can be enrolled, but should admitted to use anti-virus drugs such as entecavir, tenofovir, etc, and supervisory the relative indication during the treatment.
- •Had big lesion(single lesion diameter ≥7.5 cm).
Arms & Interventions
ThisCART19A cell injection
In this study, allogeneic anti-CD19 CART cell (This CART19A) injection is used to treat patients with refractory or relapsed CD19 positive B cell Lymphoma.
Intervention: ThisCART19A
Outcomes
Primary Outcomes
Dose limited toxicity(DLT) observation in patient with NHL during dose escalation stage
Time Frame: 28 days
DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level.
The incidence of all grade TEAEs and ≥3 grade TEAEs during dose escalation stage
Time Frame: Up to 2 years after ThisCART19A infusion
Incidence of treatment-emergent adverse events (TEAEs) and ≥3 grade TEAEs
Objective Response Rate in patient with NHL during dose expansion stage
Time Frame: 12 months
the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment
Secondary Outcomes
- Analysis the severity and Incidence of Adverse Events in each dose level during dose escalation and dose expansion stage(3 months)
- Analysis the change characteristics of CART cell number and copy number during dose escalation and expansion stages(6 months)
- the change characteristics of immune effect cells number during dose escalation and expansion stages(3 months)
- Analysis the change characteristics of cytokines during dose escalation and expansion stages (IL-1β/IL-2/IL-4/IL-5/IL-6/IL-8/IL-10/IL-12p70/IL-17A/IL-17F/IL-22/TNF-α/TNF-β)(3 months)
- Duration of response (DOR) during dose escalation stage and expansion stage(12 months)
- Progress-free survival (PFS) during dose escalation stage and expansion stage(12 months)
- OS(overall survival) during dose escalation stage and expansion stage(12 months)