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

Phase 1

Terminated

• Conditions: Mantle Cell Lymphoma; Diffuse Large B Cell Lymphoma; Follicular Lymphoma; Small Lymphocytic Lymphoma
• Interventions: Drug: LUCAR-20S CAR-T cells

• Registration Number: NCT04176913
• Lead Sponsor: The First Affiliated Hospital with Nanjing Medical University

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.

Study Timeline

• Study First Submitted: 2019-11-18
• Study First Submitted QC: 2019-11-22
• Study First Posted: 2019-11-25
• Study Start: 2020-12-01
• Status Verified: 2021-12
• Primary Completion: 2021-12-09
• Study Completion: 2021-12-09
• Last Update Submitted: 2021-12-17
• Last Update Posted: 2022-01-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 7

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Anti-CD20 Allogeneic CAR-T Cell Therapy	LUCAR-20S CAR-T cells	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.

Primary Outcome Measures

Name	Time	Method
Dose limiting toxicity (DLT)	30 days post infusion	DLT assessed by NCI-CTCAE 5.0
Concentration of Pharmacokinetics in blood	through study completion, 2 years after infusion of the last subject	PK CAR positive T cells in peripheral blood, PK CAR transgene levels in peripheral blood
Adverse events	90 days post infusion	Incidence and severity of adverse events as assessed by NCI-CTCAE 5.0
Concentration of Pharmacokinetics in bone marrow	through study completion, 2 years after infusion of the last subject	PK CAR positive T cells in bone marrow, PK CAR transgene levels in bone marrow

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR) after administration	3 months post infusion	Antitumor efficacy by 2014 Lugano criteria
Progress Free Survival (PFS) after administration	through study completion, 2 years after infusion of the last subject	Antitumor efficacy by 2014 Lugano criteria
Recommended Phase II dose (RP2D)	30 days post infusion	RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion
Time to Response (TTR) after administration	3 months post infusion	Antitumor efficacy by 2014 Lugano criteria
Duration of remission (DOR) after administration	through study completion, 2 years after infusion of the last subject	Antitumor efficacy by 2014 Lugano criteria
Overall Survival (OS) after administration	through study completion, 2 years after infusion of the last subject	Antitumor efficacy by 2014 Lugano criteria

Trial Locations

Locations (3)

Hematological Department, People's Hospital of Jiangsu Province; 🇨🇳 Nanjing, Jiangsu, China

Oncology Department，The First Affiliated Hospital of USTC west district; 🇨🇳 Hefei, Anhui, China

Hematological Department，Beijing Boren Hospital; 🇨🇳 Beijing, China