Clinical trial NCT04169932: The Clinical Study of CD20 CAR-T Cells in Patients With Relapsed and Refractory B Cell Non-Hodgkin Lymphoma
Official title: The Clinical Study of CD20 CAR-T Cells in Patients With Relapsed and Refractory B Cell Non-Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Relapsed and Refractory B Cell Lymphoma
Non-Hodgkin Lymphoma
Keywords: CD20 CAR T Cells
Safety, tolerance and efficacy
Lead sponsor: Shanghai Longyao Biotechnology Inc., Ltd.
Sponsor class: OTHER
First posted: 2019-11-20
Enrollment: 20
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, open-label study to evaluate the safety, tolerance and efficacy of CD20 CAR-T Cells in patients with relapsed and refractory B cell non-Hodgkin Lymphoma. Subjects receive a single intravenous infusion of CD20-CART cells per treatment course.

Detailed description: The maximum dose was determined according to the dose escalation test. Based on the number of CART cells per kg body weight which was proved to be safe and effective, all the subjects were treated with one single dose of CD20 CART cells per treatment course. The dose escalation test was designed to evaluate the four dose levels of CD20-CART (1 × 10 \^ 6 cells/kg,2 × 10 \^ 6 cells/kg,4 × 10 \^ 6 cells/kg,8 × 10 \^ 6 cells/kg). Each CD20-CART infusion will be carried out on day 0. Each subject was observed for at least 4 weeks after the last infusion. If there was no dose-limited toxicity (DLT), it is necessary to continue multiple treatment courses at this dose level. The detailed administration time and dose were decided by the researchers. The observation period was 4 weeks after the end of the course of treatment. If 2 or more cases of DLT occurred at a certain dose level, the prior dose level was the maximum tolerable dose of (MTD). If one case of DLT occurred, 3 subjects were added to the group. If there were no DLT in 3 cases, the next dose level would be estimated. If at least 1 case of DLT occurred in the 3 cases, the prior dose was the maximum tolerated dose of (MTD). If there were no DLT at the maximum dose, the maximum tolerant dose was the maximum dose.

Eligibility criteria: Inclusion Criteria:

* 1. Patients with CD20+ relapsed or refractory B cell Non-Hodgkin lymphoma, which includes but not limited to diffuse large B cell lymphoma (DLBCL), follicular lymphoma, transformed follicular lymphoma, marginal-zone lymphoma, mantle-cell lymphoma, small B-cell lymphoma, are eligible for inclusion in this study must meet one of the following criteria:

  1. Relapsed or refractory as defined by not achieving a PR after a second-line drug therapy such as CD20 monoclonal antibodies, or achieving a PR but the disease has progressed, or chieving a CR but the disease has relapsed.
  2. Relapse after autologous stem cell transplantation (SCT) within 1 year.
* 2. Adult subjects between 18 and 70 years of age, inclusive.
* 3. Life expectancy \> 3 months.
* 4. ECOG score between 0 and 1.
* 5. Liver, Renal, Heart and Lungs function defined as:

  1. Creatininec≤1.5 ULN;
  2. ALT/AST ≤2.5 ULN;
  3. Total Bilirubin≤1.5×ULN;
  4. Pulse oxygenation≥92%;
  5. Left Ventricular Shortening Fraction (LVSF)≥50%;
  6. Echocardiogram (ECHO) shows no obvious pericardial effusion.
* 6. According to Lugano 2014 criteria for assessing FDG-PET/CT in lymphoma, the lesions must meet the minimum size requirement of being \>15 mm in longest diameter (LDi).
* 7. Subjects could comprehend the clinical study and able to provide written consent at the time of consent or assent.

Exclusion Criteria:

* 1. Pregnant or lactating women, or women with pregnancy plans within 6 months.
* 2. HBsAg or the titer of HBV was not in the range of normal reference value; positive for presence of HCV antibody or HCV RNA in peripheral blood; positive for presence of human immunodeficiency virus type 1 or 2 (HIV-1 or HIV-2).
* 3. Severe heart disease: include but not limited to Unstable angina pectoris, myocardial infarction (within 6 months before screening), Congestive heart failure (New York Heart Association \[NYHA\] Classification ≥ III).
* 4. Previously received other CART therapy or transgenic cell therapy.
* 5. The subjects participated in clinical trials within 6 months before screening.
* 6. Subjects who were receiving systemic steroid therapy and determined by the researchers to require long-term use of systemic steroid therapy except for inhalation or local use before screening.
* 7. Subjects who had more than 2 years of autoimmune disease history (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) that caused organ damage or subjects who needed to take systemic immunosuppressants;
* 8. Any unstable systemic disease, including but not limited to, liver, kidney or metabolic diseases requiring drug treatment.
* 9. Autologous transplantation or allotransplantation was performed within 6 months after admission.
* 10. Evidence or history of central nervous system involvement in lymphoma.
* 11. Subjects with active bleeding caused by the involvement of the original lesion in the digestive tract.
* 12. Subjects with active infectious diseases who received systematic antibiotic treatment within 2 weeks of admission.
* 13. Other subjects judged by the researchers to be unsuitable for admission to the study.

Primary outcomes:
measure: The Adverse events (AEs)
timeFrame: 4 weeks
measure: Expression of CD20 CART cells
timeFrame: 2 years
measure: Detection of CD20 CART cells
timeFrame: 2 years
measure: Graft Activity Endpoint Detection
timeFrame: 2 years
Secondary outcomes:
measure: Overall remission rate (ORR)
timeFrame: 2 years
measure: Complete Remission (CR)
timeFrame: 2 years
measure: Partial Remission (PR)
timeFrame: 2 years
measure: To evaluate the duration of remission (DOR)
timeFrame: 2 years
measure: To evaluate the Progression-free survival (PFS)
timeFrame: 2 years
measure: To evaluate the Overall survival (OS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Nanjing
country: China
facility: The First Affiliated Hospital with Nanjing Medical University
state: Jiangsu
Study officials:
affiliation: Shanghai Longyao Bio-Tech Co., Ltd.
name: Yi Yao, ph.D
role: STUDY_CHAIR
References: