Clinical trial NCT04176913: Study of LUCAR-20S in Patients With R/R NHL
Official title: A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of LUCAR-20S in Patients With Relapsed/Refractory Diffuse Large B-Cell, Follicular, Mantle Cell or Small Lymphocytic Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Diffuse Large B Cell Lymphoma
Follicular Lymphoma
Mantle Cell Lymphoma
Small Lymphocytic Lymphoma
Lead sponsor: The First Affiliated Hospital with Nanjing Medical University
Sponsor class: OTHER
Collaborators: name: Nanjing Legend Biotechnology Co.,Ltd.; The First Affiliated Hospital of USTC west district; Beijing Boren Hospital
First posted: 2019-11-25
Enrollment: 7
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: An open label, single arm Phase I study to evaluate the safety, tolerability, and pharmacokinetics of LUCAR-20S CAR-T cells in relapsed or refractory CD20+ diffuse large B-cell, follicular, mantle cell and small lymphocytic lymphoma.

Detailed description: This study is an open, dose escalation/dose regimen finding study to assess the safety and pharmacokinetics of donor-derived CD20-directed CAR-T cells administered with lymphodepletion, and to obtain the preliminary efficacy results in subjects who have been diagnosed with relapsed or refractory CD20 positive diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma or small lymphocytic lymphoma. The allo-CAR-T cells will be infused in single-dose.

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent form (ICF)
2. Age 18 Years to 75 Years
3. Pathological diagnosis of refractory/relapsed CD20+ non-Hodgkin's lymphoma (one of the following):

   1. Diffuse large B-cell lymphoma (DLBCL)
   2. Follicular lymphoma (FL)
   3. Mantle cell lymphoma (MCL)
   4. Small lymphocytic lymphoma (SLL)
4. Measurable disease as defined by 2014 Lugano criteria at Screening
5. Refractory/relapsed disease after standard-of- care treatment as following (Undergone at least 2 complete cycle of therapy for each line, unless PD been documented as the best response to the regimen) and not eligible or appropriate for HSCT (Auto/allo). Subject must have documented evidence of progressive disease on or within 12 months of their last regimen.

   1. DLBCL: Refractory/relapsed after at least 1 prior line of therapy, must have been treated with anti-CD20 monoclonal antibody
   2. FL: Refractory/relapsed after at least 2 prior lines of therapy, must have been treated with anti-CD20 monoclonal antibody
   3. MCL: Refractory/relapsed after at least 2 prior lines of therapy
   4. SLL: Refractory/relapsed after at least 2 prior lines of therapy
6. Laboratory criteria at Screening

   ① Blood routine: NE≥1.0×109/L；HGB≥8g/dL；PLT≥50×109/L

   ② Blood biochemical parameters:
   1. Total bilirubin ≤ 1.5 times of the normal upper limit (ULN)
   2. Aspartate and alanine aminotransferases (AST, ALT) ≤ 3 times ULN (in the presence of liver metastasis, ULN 5 times)
   3. Estimated glomerular filtration rate (eGFR) \> 60mL/min
7. Life expectancy \> 12 weeks
8. Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1

Exclusion Criteria:

1. Any malignancy besides the NHL categories under study, exceptions include

   1. Any other malignancy curatively treated and disease-free for at least 2 years prior to enrollment
   2. History of non-melanoma skin cancer with sufficient treatment and currently no evidence of recurrence
2. Prior treatment with an allogeneic stem cell transplant
3. Prior treatment with genetic therapy
4. Prior treatment with chimeric antigen receptor T (cells) CAR-T therapy directed at CD20 target
5. Those who are positive for any index of hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), and human immunodeficiency virus antibody (HIV-Ab)
6. Prior antitumor therapy with insufficient washout period

   1. Targeted therapy, epigenetic therapy, experimental drug therapy or experimental invasive treatment with medical apparatus and instruments 14 days or five half-lives, whichever is shorter before lymphodepletion
   2. Use of monoclonal antibodies 21 days prior to lymphodepletion
   3. Chemotherapy within 14 days prior to lymphodepletion
   4. Radiotherapy within 14 days prior to lymphodepletion
   5. Participated in other clinical trials within 30 days prior to lymphodepletion
7. With central nervous system involvement
8. Women in pregnancy or lactation
9. Being fertile and unable to use effective conception during treatment and 100 days after CAR-T infusion
10. Active autoimmune disease or history of autoimmune disease within 3 years
11. With obvious hemorrhagic tendency such as gastrointestinal hemorrhage, coagulation disorders and hypersplenism
12. The following cardiac conditions

    1. New York Heart Association (NYHA) stage III or IV congestive heart failure
    2. Left ventricular ejection fraction (LVEF) less than (\<)45%
    3. Uncontrolled cardiac arrhythmia post-medication
    4. With a history of myocardial infraction or unstable angina pectoris within the past 6 months
    5. Constrictive pericarditis
    6. Cardiomyopathy
13. Pulse oximetry of \<96% on room air
14. Active or uncontrolled infection requiring parenteral antibiotics, or any evidence of severe active viral/bacterial infection or uncontrolled systemic fungal infection
15. Uncontrolled diabetes mellitus, defined as fast serum glucose \> 1.5 times ULN
16. Concurrent use of corticosteroids or other immunosuppressant medications for chronic disease
17. Concurrent use of hematopoietic growth factor
18. Stroke or seizure within 6 months of signing ICF
19. Have received any live, attenuated vaccine within 4 weeks prior to lymphodepletion
20. Have underwent major surgical operation within 2 weeks prior to lymphodepletion, or anticipate to undergo a major surgical operation during the study process or within 2 weeks posterior to study treatment(with the exception of anticipated local anesthesia surgery)
21. Known life threatening allergies, hypersensitivity, or intolerance to LUCAR-20S CAR-T cells or its excipients, including dimethyl sulfoxide (DMSO)
22. Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol

Primary outcomes:
measure: Dose limiting toxicity (DLT)
timeFrame: 30 days post infusion
measure: Adverse events
timeFrame: 90 days post infusion
measure: Concentration of Pharmacokinetics in blood
timeFrame: through study completion, 2 years after infusion of the last subject
measure: Concentration of Pharmacokinetics in bone marrow
timeFrame: through study completion, 2 years after infusion of the last subject
Secondary outcomes:
measure: Recommended Phase II dose (RP2D)
timeFrame: 30 days post infusion
measure: Overall response rate (ORR) after administration
timeFrame: 3 months post infusion
measure: Time to Response (TTR) after administration
timeFrame: 3 months post infusion
measure: Duration of remission (DOR) after administration
timeFrame: through study completion, 2 years after infusion of the last subject
measure: Progress Free Survival (PFS) after administration
timeFrame: through study completion, 2 years after infusion of the last subject
measure: Overall Survival (OS) after administration
timeFrame: through study completion, 2 years after infusion of the last subject
Other outcomes:
Locations:
city: Hefei
country: China
facility: Oncology Department，The First Affiliated Hospital of USTC west district
state: Anhui
city: Nanjing
country: China
facility: Hematological Department, People's Hospital of Jiangsu Province
state: Jiangsu
city: Beijing
country: China
facility: Hematological Department，Beijing Boren Hospital
Study officials:
affiliation: The first Affiliated Hospital Of Nanjing Medical University(JiangSu Province Hospital)
name: Wei Xu, PhD& MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Anhui Provincial Cancer Hospital
name: Kaiyang Ding, PhD& MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Beijing Boren Hospital
name: Kai Hu, PhD& MD
role: PRINCIPAL_INVESTIGATOR
References: