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

Non-Hodgkin's Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05349266
• Other study ID #: FT400-003
• Status: Recruiting
• Phase: Phase 1
• Start date: March 18, 2022
• Est. completion date: April 30, 2024

Study information

• Verified date: April 2022
• Source: Zhejiang University
• Contact: Ming Ming Zhang, Doctor
• Phone: 13656674208
• Email: mingmingzhang[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 16
• Est. completion date: April 30, 2024
• Est. primary completion date: March 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin's Lymphoma

Intervention

Biological:
• ThisCART19A
each patient will receive a dose level per body weight(kg) for only once.

Locations

Country	Name	City	State
China	The first affiliated hospital of medical college of zhejiang university	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limited toxicity(DLT) observation in patient with NHL during dose escalation stage	DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level.	28 days
Primary	Objective Response Rate in patient with NHL during dose expansion stage	the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment	12 months
Secondary	Objective Response Rate during dose escalation stage and expansion stage	the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable (UE) as best response to treatment	12 months
Secondary	Duration of response(DOR) during dose escalation stage and expansion stage	The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR)	12 months
Secondary	OS(overall survival) during dose escalation stage and expansion stage	Overall survival (OS) is defined as the time from the date of lymphodepletion until death from any cause.	12 months
Secondary	Time to remission(TTR) during dose escalation stage and expansion stage	Time to remission(TTR) is defined as the time from the date of ThisCART19A infusion until the date of first remission.	12 months
Secondary	Analysis the change characteristics of CART cell number and copy number during dose escalation and expansion stages	Track CAR T cells expansion in patients after infusion	6 months
Secondary	Analysis the change characteristics of cytokines and immune effect cells number during dose escalation and expansion stages	Analysis the effect cells and cytokines in patient after infusion	3 months
Secondary	Analysis the severity and Incidence of Adverse Events in each dose level during dose expansion stage	Including more than or equal to grade 3 adverse events graded according to the NCI CTCAE v5.0, or the adverse events with special attention	3 months
Secondary	Analysis the immunogenicity(anti-therapeutic antibody and neutralizing antibody) of CAR-T cells after infusion		12 months