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
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ThisCART19A 2×10^6 cells/kg for dose level 1 Patients will receive 2×10^6 cells/kg of ThisCART19A |
Biological: ThisCART19A
each patient will receive a dose level per body weight(kg) for only once.
|
| Experimental: ThisCART19A 3×10^6 cells/kg as dose level 2 Patients will receive 3×10^6 cells/kg of ThisCART19A |
Biological: ThisCART19A
each patient will receive a dose level per body weight(kg) for only once.
|
| Experimental: Patients will receive 4×10^6 cells/kg as dose level 3 Patients will receive 4×10^6 cells/kg of ThisCART19A |
Biological: ThisCART19A
each patient will receive a dose level per body weight(kg) for only once.
|
Outcome Measures
Primary Outcome Measures
- Dose limited toxicity(DLT) observation in patient with NHL during dose escalation stage [28 days]
DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level.
- Objective Response Rate in patient with NHL during dose expansion stage [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 Outcome Measures
- Objective Response Rate during dose escalation stage and expansion stage [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
- Duration of response(DOR) during dose escalation stage and expansion stage [12 months]
The duration of overall response is measured from the time measurement criteria are met for complete response (CR) or partial response (PR)
- OS(overall survival) during dose escalation stage and expansion stage [12 months]
Overall survival (OS) is defined as the time from the date of lymphodepletion until death from any cause.
- Time to remission(TTR) during dose escalation stage and expansion stage [12 months]
Time to remission(TTR) is defined as the time from the date of ThisCART19A infusion until the date of first remission.
- Analysis the change characteristics of CART cell number and copy number during dose escalation and expansion stages [6 months]
Track CAR T cells expansion in patients after infusion
- Analysis the change characteristics of cytokines and immune effect cells number during dose escalation and expansion stages [3 months]
Analysis the effect cells and cytokines in patient after infusion
- Analysis the severity and Incidence of Adverse Events in each dose level during dose expansion stage [3 months]
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
- Analysis the immunogenicity(anti-therapeutic antibody and neutralizing antibody) of CAR-T cells after infusion [12 months]
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The first affiliated hospital of medical college of zhejiang university | Hangzhou | Zhejiang | China | 310003 |
Sponsors and Collaborators
- Zhejiang University
Investigators
- Principal Investigator: He Huang, Doctor, First hospital affiliated Zhejiang University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- FT400-003