A PhaseⅠb Study Evaluating Safety and Efficacy of C-CAR011 Treatment in B- NHL Subjects

A Phase Ⅰb Study Evaluating Safety and Efficacy of Anti-CD19 Chimeric Antigen Receptor T-cell (C-CAR011) Treatment in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

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).

The study will include the following sequential phases: Screening, Pre- Treatment (Cell Product Preparation; Lymphodepleting Chemotherapy), Treatment and Follow-up

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.