Clinical trial NCT04661020: CD19 CAR-T Therapy for Patients With B-cell Non-Hodgkin's Lymphoma
Official title: Clinical Trial for the Safety and Efficacy of CD19 CAR-T Therapy for Patients With B-cell Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-hodgkin Lymphoma,B Cell
Keywords: Non Hodgkin Lymphoma
CAR T-cell therapy
CD19
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2020-12-09
Enrollment: 36
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 Study of CD19 CAR-T Therapy for Patients With B-cell Non-Hodgkin's Lymphoma.

Detailed description: This is a single arm, open-label, single-center study. This study is indicated for patients with CD19+ non-Hodgkin's lymphoma. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 36 patients will be enrolled. Primary objective is to explore the safety, main consideration is dose-related safety.

Eligibility criteria: Inclusion Criteria:

1. Age no less than 18, no gender limit;
2. Histologically confirmed diagnosis of HGBCL（HGBCL-NOS、HGBCL involving combined rearrangements of MYC, bcl-2 and bcl-6）DLBCL、not otherwise specified and IPI≥3;
3. Newly diagnosed B-NHL, unwilling to receive RCHOP first- or second-line chemotherapy, but willing to receive targeted drugs (such as a regimen consisting of CD20 monoclonal antibody，lenalidomide and Brutons tyrosine kinase inhibitor for two courses) as preconditioning regimens for CAR-T cell therapy;
4. Patients with PR or SD efficacy evaluated by PET-CT after two courses of tumor reduction therapy;
5. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L;
6. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;
7. No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;
8. Estimated survival time ≥ 3 months;
9. ECOG performance status 0 to 2;
10. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.

Exclusion Criteria:

1. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
3. Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
4. Active infection of hepatitis B virus or hepatitis C virus;
5. Previously treated with any CAR-T cell product or other genetically modified T cell therapies;
6. Insufficient amplification capacity in response to CD3 / CD28 co-stimulus signal (\<5 times) ;
7. Creatinine\>2.5mg/dl, or ALT / AST \> 3 times of normal amounts, or bilirubin\>2.0 mg/dl;
8. Other uncontrolled diseases that were not suitable for this trial;
9. Patients with HIV infection;
10. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 28 days after CD19 targeted CAR T-cells infusion
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 2 years after CD19 targeted CAR T-cells infusion
Secondary outcomes:
measure: B-cell Non-Hodgkin's Lymphoma (B-NHL), Overall response rate (ORR)
timeFrame: At Month 1, 3, 6, 12, 18 and 24
measure: B-NHL, Overall survival (OS)
timeFrame: Up to 2 years after CD19 CAR-T cells infusion
measure: B-NHL, Event-free survival (EFS)
timeFrame: Up to 2 years after CD19 CAR-T cells infusion
measure: Quality of life(EORTC QLQ-C30) Core 30 (EORTC QLQ-C30)
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Activities of Daily Living (ADL) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Instrumental Activities of Daily Living (IADL) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Hospital Anxiety and Depression Scale (HADS) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital，College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
References: