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

This is an interventional treatment trial for B-cell Non-Hodgkin Lymphoma focused on measuring B-cell Non-Hodgkin Lymphoma, Refractory, Relapsed Read More

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.