Study of LUCAR-20S in Patients With R/R NHL

Mantle Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04994587
• Other study ID #: BRYY-IIT-LCYJ-2021-012
• Secondary ID: BM2L201904
• Status: Recruiting
• Phase: Phase 1
• Start date: December 1, 2020
• Est. completion date: January 21, 2023

Study information

• Verified date: July 2021
• Source: Beijing Boren Hospital
• Contact: Kai Hu, MD/PhD
• Phone: +8615010390336
• Email: xiaohu7079[@]sina.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Using an accelerated titration design combined with BOIN design using live CAR-positive T cells at a starting dose of 0.17×106/kg(range 0.12 to 0.22×106/kg), 6 dose groups [0.17×106/kg(range 0.12~0.22×106/kg), 30×106, 90×106, 300×106, 600×106 and 900×106 live CAR positive T cells were evaluated to determine MTD or RP2D for LUCAR-20S cells. In the medium group, 0.17×106/kg(range 0.12~0.22×106/kg), 30×106, 90×106 live CAR positive T cells; The BOIN phase dose group consisted of 300×106, 600×106 and 900×106 live CAR positive T cells. To avoid exposing more subjects to the invalid dose group, DLT was first explored by accelerated titration after the trial began. There were about 24 subjects at this stage.

In the dose expansion phase, more subjects were enrolled at established MTD or RP2D doses to further evaluate the safety, tolerability, and anti-tumor efficacy of LUCAR-20S cell therapy at these doses. About 10 subjects were enrolled at this stage.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 34
• Est. completion date: January 21, 2023
• Est. primary completion date: October 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Signed informed consent form (ICF)

2. Age 18 Years to 75 Years

Pathological diagnosis of refractory/relapsed CD20+ non-Hodgkin's lymphoma (one of the following):

a. Diffuse large B-cell lymphoma (DLBCL) b. Follicular lymphoma (FL) c. Mantle cell lymphoma (MCL) d. 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.

a. DLBCL: Refractory/relapsed after at least 1 prior line of therapy, must have been treated with anti-CD20 monoclonal antibody b. FL: Refractory/relapsed after at least 2 prior lines of therapy, must have been treated with anti-CD20 monoclonal antibody c. MCL: Refractory/relapsed after at least 2 prior lines of therapy d. SLL: Refractory/relapsed after at least 2 prior lines of therapy

6. Laboratory criteria at Screening

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

• 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

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• Follicular Lymphoma
• Leukemia, Lymphocytic, Chronic, B-Cell
• Lymphoma
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Mantle-Cell
• Mantle Cell Lymphoma
• Small Lymphocytic Lymphoma

Intervention

Drug:
• LUCAR-20S CAR-T cells
An Anti-CD20 Allogeneic CAR-T Cell Therapy in Patients with Relapsed/Refractory Diffuse Large B-Cell, Follicular, Mantle Cell or Small Lymphocytic Lymphoma

Locations

Country	Name	City	State
China	Beijing Boren Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Beijing Boren Hospital	Nanjing Legend Biotech Co.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose limiting toxicity (DLT)	DLT assessed by NCI-CTCAE 5.0	30 days post infusion
Primary	Adverse events	Incidence and severity of adverse events as assessed by NCI-CTCAE 5.0	90 days post infusion
Primary	Concentration of PK CAR positive T cells in peripheral blood and bone marrow	PK CAR positive T cells in peripheral blood, PK CAR transgene levels in peripheral blood, PK CAR positive T cells in bone marrow and PK CAR transgene levels in bone marrow.	through study completion, 2 years after infusion of the last subject
Secondary	Recommended Phase II dose (RP2D)	RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion	30 days post infusion
Secondary	Overall response rate (ORR) after administration	Antitumor efficacy by 2014 Lugano criteria	3 months post infusion
Secondary	Time to Response (TTR) after administration	Antitumor efficacy by 2014 Lugano criteria	3 months post infusion
Secondary	Duration of remission (DOR) after administration	Antitumor efficacy by 2014 Lugano criteria	through study completion, 2 years after infusion of the last subject
Secondary	Progress Free Survival (PFS) after administration	Antitumor efficacy by 2014 Lugano criteria	through study completion, 2 years after infusion of the last subject
Secondary	Overall Survival (OS) after administration	Antitumor efficacy by 2014 Lugano criteria	through study completion, 2 years after infusion of the last subject