The Study of Anti-CD19 CAR NK Cells in the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma

An Exploratory Clinical Study of Safety and Efficacy of Anti-CD19 CAR NK Cells in the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma

A single arm, open-label pilot study is designed to determine the safety and effectiveness of anti-CD19 CAR NK cells in patients with B-cell Non Hodgkin Lymphoma. 9-12 patients are planned to be enrolled in the dose-escalation trial (6×10^8 cells, 1×10^9 cells, 1.5×10^9 cells). The primary endpoints are DLT, MTD. The secondary endpoints are the overall response rates (ORR) and disease control rate (DCR).

Study Overview

• Status: Recruiting
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Biological: anti-CD19 CAR NK cells

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jianmin Yang, Ph. D.; Phone Number: 13918735105; Email: chyangjianmin@163.com
• Study Contact Backup: Name: Libing Wang, Ph.D.; Phone Number: 13918735105; Email: doctorwanglibing@126.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Changhai Hospital
    • Contact: Jianmin Yang, Doctor; Phone Number: 86-18317172636; Email: yangjianmin@csco.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects voluntarily participate in this clinical study and sign the Informed Consent Form (ICF).
2. Clinical diagnosis of CD19 positive diffuse large B cell lymphoma as defined by the 2017 World Health Organization (WHO) classification of tumors of haematopoietic and lymphoid tissue.
3. Relapsed/Refractory diffuse large B cell lymphoma refers to: not complete response (CR) of 2 lines of standard treatment; PD after treatment or duration of SD less than 6 months after treatment; progress or relapse within 12 months after autologous stem cell transplant.
4. Subjects with a measurable or evaluable lesion (more than one lesion≥15mm) according to IWG criteria.
5. Age≥ 18 years old and ≤ 75 years old, male or female.
6. Subjects with estimated survival > 12 weeks.
7. Serum albumin (ALB) ≥30g/L, Total Bilirubin (TBIL) ≤ 25.7μmol/L, serum creatinine (SCr) ≤ 132.6μmol/L, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 times the upper limit of normal (ULN).
8. Absolute neutrophil count (ANC) ≥ 1.0×109/L, platelet count ≥ 50×109/L.
9. ECOG performance ≤ 1.
10. Left ventricular ejection fraction (LVEF) ≥50% and no clinically significant pericardial effusion.
11. ≥ 4 weeks after subjects received last dose treatment (Radiotherapy, chemotherapy, monoclonal antibody therapy or other treatments).

Exclusion Criteria:

1. Subjects with known severe allergic reactions, hypersensitivity, contraindication to any medications during the trial (cyclophosphamide, fludarabine, tozumabs), or subjects with a history of severe allergic reactions.
2. Relapsed after allogenic haemopoietic stem cell transplantation (HSCT).
3. Subjects with active infection receiving intravenous (IV) antibiotic treatment, or received intravenous (IV) antibiotic treatment within one week prior to anti-CD19 CAR NK Cell infusion.
4. Subjects with acquired and congenital immunodeficiency diseases.
5. Subjects with grade III or IV heart failure (NYHA classification).
6. History of epilepsy or other central nervous system (CNS) diseases.
7. Subjects with extranodal lymphoma in Intracranial, lung, or gastrointestinal tract.

8. History of other primary malignant tumors except:

   1. Cured non-melanoma skin cancer by surgical excision, for example basal cell carcinoma (BCC);
   2. Cured primary malignant tumors, such as cervical cancer, superficial bladder cancer, breast cancer.
9. Systemic corticosteroids are used concomitantly within 2 weeks prior to treatment.
10. Females who are pregnant, lactating, or planning a pregnancy within six months.
11. Subjects who have received other clinical trial treatment within 3 months.
12. Any situation judged by the investigators that may increase the risk of the subjects or interfere with the clinical trial outcome.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: anti-CD19 CAR NK cells; CD19-CAR-NK is an allogenic CD19-Targeted chimeric antigen receptor NK-cell (CAR-NK) therapy.	Biological: anti-CD19 CAR NK cells; Patients will receive Fludarabine (30 mg/m2 per day) and Cyclophosphamide (300mg/m2 per day) on day -5, -4, and -3. Doses of 6×10^8, 1×10^9, 1.5×10^9 Anti-CD19 CAR NK cells will infused in each group using the "3 + 3" dose-escalation strategy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limiting toxicity (DLTs)	To characterize the safety, tolerability, and determine the Maximum tolerated dose (MTD) of Anti-CD19 CAR NK Cells for Relapsed/Refractory diffuse large B cell lymphoma.	within 4 weeks after infusion
Incidence of Treatment Emergent Adverse Events (TEAEs)	To characterize the safety of Anti-CD19 CAR NK Cells for Relapsed/Refractory diffuse large B cell lymphoma	up to 48 weeks after infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease control rate (DCR)	To characterize the efficacy of Anti-CD19 CAR NK Cell Therapy for R/R Non-Hodgkin Lymphoma.	1, 3, 6, 12 and 12 months after infusion
The overall response rate (ORR)	To characterize the efficacy of Anti-CD19 CAR NK Cell Therapy for Relapsed/Refractory diffuse large B cell lymphoma	1, 3, 6 and 12 months after infusion

Collaborators and Investigators

• Sponsor: Changhai Hospital
• Collaborators: Nanjing Enricnk Biotech Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Estimated): December 30, 2023
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: December 21, 2022
• First Posted (Actual): January 6, 2023

Study Record Updates

• Last Update Posted (Actual): August 28, 2023
• Last Update Submitted That Met QC Criteria: August 25, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: CD19; CAR-NK; B-Cell Lymphoma; diffuse diffuse large B cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
• Other Study ID Numbers: CHEC2022-251

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No