Clinical trial NCT05349266: Assessment of Safety and Efficacy of ThisCART19A in Adult Patients With B-NHL After Failure of Autologous Chimeric Antigen Receptor T- Cell(CAR-T) Therapy
Official title: Assessment of Safety and Efficacy of ThisCART19A in Adult Patients With B Cells Non-Hodgkin's Lymphoma(B-NHL) After Failure of Autologous CAR-T Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Non-Hodgkin's Lymphoma
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2022-04-27
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a phase I, single center study to assess the efficacy and safety of ThisCART19A in adult with Non-Hodgkins Lymphoma in China.


Eligibility criteria: Inclusion Criteria:

* Cellular or histopathological diagnosis of B-cell non-Hodgkin's lymphoma (B-NHL) includes: diffuse Large B-cell lymphoma (DLBCL), follicular lymphoma to DLBCL (tFL), follicular lymphatic (FL), Mantle cell lymphoma (MCL), primary Mediastinal Large B-cell lymphoma (PMBCL), etc.
* Failing to autologous CAR-T therapy.
* At least one available lesion to be assessed.
* Good organ function during screening.
* Should be confirmed Cluster of differentiation(CD)19 positive by biopsy for the patient who received target CD19 therapy before.

Exclusion Criteria:

* Allergic to preconditioning measures.
* 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 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 ≥10 cm).
* Bone marrow involvement≥5%.
* Receive allogeneic hematopoietic stem cell transplantation less than 100 days.
* Combined systemic steroid use (e.g., prednisone ≥20mg) within 3 days prior to screening. Or systemic diseases that require long-term use of immunization Inhibitor.
* Vaccinated with influenza vaccine within 2 weeks prior to lymphodepleting chemotherapy (Severe Acute Respiratory Syndrome-Corona virus disease 19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included) .
* Patients who are receiving Graft versus host disease Hepatitis(GvHD) treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion.
* Women who are in pregnant or lactating, and female subjects or partners who plan to be pregnant within 1 year after cell infusion. Male subjects who plan pregnancy within 1 year after infusion.

Primary outcomes:
measure: Dose limited toxicity(DLT) observation in patient with NHL during dose escalation stage
timeFrame: 28 days
measure: Objective Response Rate in patient with NHL during dose expansion stage
timeFrame: 12 months
Secondary outcomes:
measure: Objective Response Rate during dose escalation stage and expansion stage
timeFrame: 12 months
measure: Duration of response(DOR) during dose escalation stage and expansion stage
timeFrame: 12 months
measure: OS(overall survival) during dose escalation stage and expansion stage
timeFrame: 12 months
measure: Time to remission(TTR) during dose escalation stage and expansion stage
timeFrame: 12 months
measure: Analysis the change characteristics of CART cell number and copy number during dose escalation and expansion stages
timeFrame: 6 months
measure: Analysis the change characteristics of cytokines and immune effect cells number during dose escalation and expansion stages
timeFrame: 3 months
measure: Analysis the severity and Incidence of Adverse Events in each dose level during dose expansion stage
timeFrame: 3 months
measure: Analysis the immunogenicity(anti-therapeutic antibody and neutralizing antibody) of CAR-T cells after infusion
timeFrame: 12 months
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The first affiliated hospital of medical college of zhejiang university
state: Zhejiang
Study officials:
affiliation: First hospital affiliated Zhejiang University
name: He Huang, Doctor
role: PRINCIPAL_INVESTIGATOR
References: