Clinical trial NCT05436223: Human CD19 Targeted T Cells Injection(CD19 CAR-T) Therapy for Relapsed and Refractory B-cell Non-Hodgkin's Lymphoma
Official title: A Phase Ⅱ Clinical Study Evaluating the Efficacy and Safety of Human CD19 Targeted T Cells Injection (CD19 CAR-T) Therapy for Relapsed and Refractory B-cell Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: B-cell Non-Hodgkin's Lymphoma
Keywords: B-cell non-Hodgkin's Lymphoma
CD19
CAR-T
Relapsed/Refractory
Lead sponsor: Hrain Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Zhongshan Hospital
First posted: 2022-06-29
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Phase Ⅱ Clinical Study Evaluating the Efficacy and Safety of Human CD19 Targeted T Cells Injection (CD19 CAR-T) Therapy for R/R B-NHL.

Patients will be given a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of CD19 CAR+ T cells.

Detailed description: Subjects with relapsed and refractory B-cell non-Hodgkin's lymphoma would be selected if subjects meet all criteria evaluated by physical exams, blood tests, electrocardiograph, computedtomography （CT）/magnetic resonance Imaging(MRI)/positron emission tomography（PET）, tumor assessments, etc. Subjects would be hospitalized to receive the infusion of CD19 CAR+ T cells after lymphodepleting regimen, with the observation and evaluation of efficacy and safety.

Eligibility criteria: Inclusion Criteria:Subjects with relapsed/refractory B-cell non-Hodgkin's lymphoma

* Age≥18 years old，gender is not limited;
* Expected survival \> 12 weeks;
* ECOG score 0-2;
* B-cell non-Hodgkin's lymphoma confirmed by cytology or histopathology according to the 2016 World Health Organization (WHO) classification and diagnostic criteria, including: diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed filter Alveolar lymphoma (TFL) and high-grade B-cell lymphoma (HGBCL);
* Pathology demonstrated that B-cell non-Hodgkin's lymphoma and who meet one of the following conditions:

  1. Relapsed and refractory B-cell non-Hodgkin's lymphoma, after standard first-line treatment and at least 2 courses of second-line treatment without remission and relapse (the previous use of CD20-targeted drugs and anthracyclines were needed);
  2. Relapse of B-cell non-Hodgkin lymphoma after stem cell transplantation, regardless of previous treatments.
* The venous access required for collection can be established and leukepheresis can be carried according to the judgement of investigators, satisfying hemoglobin≥80g/L, neutrophils ≥1.0×10\^9/L, platelets ≥75×10\^9 / L;
* According to the Lugano 2014 criteria, there should be at least one measurable tumor lesion;
* Liver, kidney and cardiopulmonary functions meet the following requirements:

  1. Serum creatinine≤1.5×ULN or creatinine clearance rate≥50mL/min (GockcroftGault formula);
  2. Cardiac ejection fraction \>50%, no clinically significant pericardial effusion detected, no clinically significant pleural effusion detected;
  3. Baseline blood oxygen saturation\>92%;
  4. Total bilirubin≤1.5×ULN(Gilbert syndrome≤5×ULN);
  5. ALT and AST≤3×ULN (AST and ALT ≤5×ULN in patients with liver metastases);
* Able to understand and sign the Informed Consent Document.

Exclusion Criteria:Any one of the following conditions cannot be selected as a subject：

* Malignant tumors other than diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (TFL), and high-grade B-cell lymphoma (HGBCL) within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, ductal carcinoma in situ after radical resection and thyroid cancer after radical resection ;
* Subjects with positive Hepatitis B surface antigen(HBsAg) or Hepatitis B core antibody (HBcAb) and positive peripheral blood hepatitis B virus (HBV) DNA titers (higher than the upper limit of the normal range of the investigative site); Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; Human Immunodeficiency Viral (HIV) antibody positive; syphilis positive;
* Any uncontrolled systemic diseases, including but not limited to active infection (except for localized infection), uncontrolled angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease;
* Any other uncontrolled active disease that precludes participation in the trial;
* Any circumstances that the investigator believes will compromise the safety of the subject or interfere with the purpose of the study;
* Pregnant or lactating woman, or planned pregnancy during treatment or within 1 year after treatment, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion;
* Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment (except uncomplicated urinary tract infection or upper respiratory tract infection);
* Subjects who were receiving systemic steroid treatment within 14 days before enrollment and who were judged by the investigator to require long-term use of systemic steroid therapy during treatment (except inhalation or topical use); or subjects who received any systemic anti-tumor therapy ( except for local anti-tumor therapy) ;
* Subjects who have received CAR-T treatment or other gene-modified cell therapy before enrollment;
* Patients with symptoms of central nervous system or brain metastasis or have received treatment for central nervous system or brain metastasis (radiotherapy, surgery or other treatment) within 3 months before enrollment;
* Subjects who have a disease that affects the signing of written informed consent or who are unable to comply with research procedures; or who are unwilling or unable to comply with research requirements;
* Subjects who are considered unsuitable to participate in this trial by the investigator.

Primary outcomes:
measure: Overall response rate (ORR) at 3 months post infusion
timeFrame: 3 months post infusion
Secondary outcomes:
measure: Duration of remission (DOR) after administration
timeFrame: 2 years post infusion
measure: Progression-free Survival (PFS) after administration
timeFrame: 2 years post infusion
measure: Overall Survival (OS) after administration
timeFrame: 2 years post infusion
measure: Disease control rate (DCR)
timeFrame: 2 years post infusion
measure: Safety evaluation
timeFrame: 2 years post infusion
measure: Pharmacokinetic (PK) parameters: Maximum CAR level inperipheral blood
timeFrame: 2 years post infusion
measure: Pharmacokinetics(PK) parameters: Time to peak CAR level in blood (Tmax)
timeFrame: 2 years post infusion
measure: Pharmacokinetics(PK) parameters: 28-day Area under the curve of the CAR level in blood(AUC0-28)
timeFrame: 2 years post infusion
measure: Pharmacodynamic (PD) parameters
timeFrame: 2 years post infusion
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan Hospital, Fudan University
state: Shanghai
Study officials:
affiliation: Shanghai Zhongshan Hospital
name: Peng Liu, M.D. & Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: