B-cell Non-Hodgkin Lymphoma
Conditions
Keywords
B-cell Non-Hodgkin Lymphoma, Refractory, Relapsed
Brief summary
This is a single arm, single-center, non-randomized study to evaluate the safety and efficacy of C-CAR011 therapy in relapsed or refractory B cell Non-Hodgkin Lymphoma (NHL).
Detailed description
The study will include the following sequential phases: Screening, Pre- Treatment (Cell Product Preparation; Lymphodepleting Chemotherapy), Treatment and Follow-up
Interventions
BIOLOGICALCD19-directed CAR-T cells
CD19-directed CAR-T cells single infusion intravenously at a target dose of 0.5-5.0 x 10\^6 anti-CD19 CAR+ T cells/kg
Sponsors
Shanghai AbelZeta Ltd.
Peking Union Medical College Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Volunteered to participate in this study and signed informed consent. * Age 18-70 years old, male or female. * Relapse or refractory B cell non-Hodgkin's lymphoma ,Histologically diagnosed as DLBCL,follicular lymphoma and Mantle cell lymphoma according to the NCCN. nonHodgkin's lymphoma Clinical Practice Guidelines (2017 Version 1) 1. DLBCL and Follicular Lymphoma (stage Ⅲ-Ⅳ, grade Ⅲb). 1. Progressive disease after the last standard chemotherapy regimens. 2. Stable disease after the last standard chemotherapy regimens(at least 4 cycles of first-line therapy or 2 cycles of later-line therapy). 3. Relapse or progressive disease within 12 months after autologous stem cell transplantation (SCT). 2. Follicular lymphoma (stage Ⅲ-Ⅳ) (gradeⅠ-Ⅲa) 1. Relapse or progressive disease within 1 year after the last standard chemotherapy regimens(At least 2 combination chemotherapy regimens). 2. Stable disease after the last standard chemotherapy regimens(at least 2 cycles of combination chemotherapy regimens). 3. Mantle cell lymphoma 1. Relapse after 1st CR or persistent disease, and not eligible or appropriate for SCT. 2. Relapse or progressive disease within 1 year after the last chemotherapy regimens(at least 4 cycles of first-line therapy or 2 cycles of later- line therapy). 3. Relapse or progressive disease within 12 months after autologous SCT. * All subjects must have received anti-CD20 monoclonal antibody (unless tumor is CD20-negative) and anthracycline-containing chemotherapy regimens according to NCCN non-Hodgkin lymphoma Clinical Practice Guidelines (2017 Version 1). * At least one measurable lesion per revised IWG Response Criteria (the longest diameter of the tumor ≥ 1.5cm). * Expected survival ≥ 12 weeks. * ECOG score 0-1. * Left ventricular ejection fraction (LVEF) ≥ 50% (detected by echocardiography). * No active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92% on room air. * At least 2 weeks from receiving previous treatment (radiotherapy or chemotherapy) prior to leukapheresis. * No contraindications of leukapheresis. * Female subjects in childbearing age, their serum or urine pregnancy test must be negative, and must agree to take effective contraceptive measures during the trial.
Exclusion criteria
* History of allergy to cellular products. * Laboratory tests: absolute neutrophil count \< 1.0 × 10\^9 /L, platelet count \< 50×10\^9 /L, serum albumin \< 30 g/L,serum bilirubin \> 1.5 ULN, serum creatinine \> ULN, ALT/AST \> 3 ULN. * History of CAR T cell therapy or any other genetically modified T cell therapy. * Relapse after allogeneic hematopoietic stem cell transplantation. * Active infections that require treatment (uncomplicated urinary tract infections and bacterial pharyngitis are allowed), prophylactic antibiotic, antiviral and antifungal treatment are permitted. * Hepatitis B or hepatitis C virus infection (including carriers), syphilis, as well as acquired or congenital immune deficiency diseases, including but not limited to HIV infection. * Class III or IV heart failure according to the NYHA Heart Failure Classifications. * QT interval prolongation ≥ 450 ms. * History of epilepsy or other central nervous system disorders. * Evidence of CNS lymphoma by head enhancement scan or magnetic resonance imaging. * History of other primary cancers, with the following exceptions. 1. Excisional non-melanoma (e.g. cutaneous basal cell carcinoma). 2. Cured in situ carcinoma (e.g. cervical cancer, bladder cancer, breast cancer). * Autoimmune diseases that require treatment, immune deficiency diseases or other diseases that require immunosuppressive therapy. * Used of systemic steroids within two weeks (using inhaled steroids is an exception). * Women who are pregnant or lactating, or who have breeding intent in 6 months. * Participated in any other clinical trial within three months. * Any situation that investigators believe the risk of the subjects is increased or results of the trial are disturbed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AE | 12 weeks | Incidence of adverse events (AEs) and serious adverse events (SAEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | 12 months | The ORR will be assessed at weeks 4 ，weeks 12 ，months 6 and months 12 |
| Duration of remission (DOR) | 12 months | The DOR will be assessed at months 12 |
| Progression free survival (PFS) | 12 months | The PFS will be assessed at months 12 |
| Overall survival rate（OSR） | 12 months | The OSR will be assessed at weeks 12 ，months 6 and months 12 |
Countries
China
Outcome results
None listed