Non-Hodgkin's Lymphoma
Conditions
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.
Interventions
BIOLOGICALThisCART19A
each patient will receive a dose level per body weight(kg) for only once.
Sponsors
Zhejiang University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 | — |
| 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 |
| 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) |
Countries
China
Contacts
Primary ContactMing Ming Zhang, Doctor
Outcome results
None listed