Exploratory Study to Evaluate Efficacy and Safety of Fast Dual CAR-T Injection in CD19+ Refractory or Relapsed B Cell Non-Hodgkinlymphoma

920th Hospital of Joint Logistics Support Force of People's Liberation Army of China0 sitesMay 5, 2021

ConditionsB-cell Lymphoma

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: B-cell Lymphoma
Sponsor: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Primary Endpoint: Incidence of AE after Fast Dual CAR-T infusion
Status: Withdrawn
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Outcomes Similar Trials

Overview

Brief Summary

This is a single arm, open-label, single-center prospective study to determine the safety and efficacy of Fast Dual CAR-T cells in patients diagnosed with CD19+ refractory/relapsed B cell non-Hodgkinlymphoma (R/R B-NHL).

Detailed Description

The main aim of the study is to determine the safety and efficacy of Fast Dual CAR-T in R/R B-NHL. Fast Dual CAR-T is an autologous dual chimeric antigen receptor T-cell (CAR-T) therapy that targets CD19 and B-cell maturation antigen (BCMA). The study will include 15 subjects to receive Fast Dual CAR-T single infusion.

Registry

clinicaltrials.gov

Start Date

May 5, 2021

End Date

December 31, 2023

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

920th Hospital of Joint Logistics Support Force of People's Liberation Army of China

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Histologically confirmed: Diffuse Large B Cell Lymphoma (DLBCL), Transformation Follicular Lymphoma (TFL), Primary Mediastinal Large B Cell Lymphoma (PMBCL) and Mantle Cell Lymphoma (MCL), High-Grade B Cell Lymphoma (HGBL);
•Refractory B-NHL: PD as the best response to normative first-line therapy (intolerance of first-line therapy is not included in this study) or SD as the best response to at least 4 courses of first-line therapy with duration no longer than 6 month from last therapy; or PD as the best response to the last therapy of second-line therapy and above,or SD as the best response to at least 2 courses of second-line therapy with duration no longer than 6 month from last therapy, or:
•Relapsed B-NHL: Histopathology confirmed relapse after standard systemic and second-line therapy achieved CR, or histopathologically confirmed relapse within 1 year after autologous hematopoietic stem cell transplantation (Not limited by previous therapy);
•Prior therapy must include anti-CD20 monoclonal antibody (unless investigator determines that tumor is CD20-negative) and an anthracycline;
•For individual with TFL, must have chemotherapy and the conform the above definition of relapse or refractory after transformation;
•According to the 2014 Lugano therapy response standard, there should be at least one measurable tumor focus: the longest diameter of nodular lesions\> 1.5 cm, and the longest diameter of extranodal lesions\> 1.0 cm;
•CD19 positive expression in tumor tissue biopsy;
•Prior to apheresis, approved anti-B-NHL therapys such as systemic chemotherapy, systemic radiotherapy and immunotherapy have been completed for at least 2 weeks;
•Eastern cooperative oncology group (ECOG) performance status of 0 to 1;
•Life expectancy ≥12 weeks;

Exclusion Criteria

•Diagnosis of other malignancy (except for cured non-melanoma skin cancer, cervical carcinoma in situ, superficial bladder cancer, ductal carcinoma in situ, or other malignancies that have completely responsed for more than 5 years);
•Severe mental disorders;
•History of hereditary diseases, including but not limited to: Fanconi anemia, Shut-Dai syndrome, Costman syndrome or any other known bone marrow failure syndrome;
•History of allogeneic stem cell transplantation;
•Grade III-IV heart failure or myocardial infarction, angioplasty or stent placement, unstableangina pectoris, or other clinically prominent heart disease within one year before enrollment.
•Have any indwelling catheter or drainage tube (such as percutaneous nephrostomy tube, indwelling catheter, bile drainage tube or pleura / peritoneum / pericardial catheter), the use of dedicated central venous catheter is allowed;
•Subjects with CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases;
•History or presence of CNS disorder, including but not limited to: seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement;
•Positive for any of the following etiological tests: HIV, HBV, HCV, TPPA;
•Presence of fungal, bacterial, viral, or other infection that is uncontrolled;

Outcomes

Primary Outcomes

Incidence of AE after Fast Dual CAR-T infusion

Time Frame: up to 24 weeks after Fast Dual CAR-T infusion

Incidence of adverse events after Fast Dual CAR-T infusion

Secondary Outcomes

ORR rate(12 weeks, 24 weeks after Fast Dual CAR-T infusion)
OS(12 weeks, 24 weeks after Fast Dual CAR-T infusion)
PFS(12 weeks, 24 weeks after Fast Dual CAR-T infusion)
Changes in the concentration of cytokine IL-1, IL-2, IL-6, IL-10, TNF-α and IFN-γ.(Days 4, 7, 10, 14 and 28 after Fast Dual CAR-T infusion)
Change of CAR Copies(Days 4, 7, 10, 14 and weeks 4, 8, 12, 18, 24 after Fast Dual CAR-T infusion)
Change of RCL in blood(Weeks 4, 12, 24 after Fast Dual CAR-T infusion)
Change of CAR-T cell counts(Days 4, 7, 10, 14 and weeks 4, 8, 12, 18, 24 after Fast Dual CAR-T infusion)