Clinical trial NCT03483688: A PhaseⅠb Study Evaluating Safety and Efficacy of C-CAR011 Treatment in B- NHL Subjects
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: B-cell Non-Hodgkin Lymphoma
Keywords: B-cell Non-Hodgkin Lymphoma
Refractory
Relapsed
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai AbelZeta Ltd.
First posted: 2018-03-30
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: AE
timeFrame: 12 weeks
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: 12 months
measure: Duration of remission (DOR)
timeFrame: 12 months
measure: Progression free survival (PFS)
timeFrame: 12 months
measure: Overall survival rate（OSR）
timeFrame: 12 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijing
Study officials:
affiliation: Peking Union Medical College Hospital
name: Daobin Zhou
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang L, Zhang Y, Zhou DB. [Anti-CD19 CART (C-CAR011) Therapy for Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2021 Aug;29(4):1141-1147. doi: 10.19746/j.cnki.issn.1009-2137.2021.04.019. Chinese.