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

NCT05673447 | Unknown Early Phase 1

• 1 other identifier: CHEC2022-251
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Diffuse Large B Cell Lymphoma

Keywords

B-Cell Lymphoma; CD19; CAR-NK; diffuse diffuse large B cell lymphoma

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• The overall response rate (ORR)

  1, 3, 6 and 12 months after infusion

• Disease control rate (DCR)

  1, 3, 6, 12 and 12 months after infusion

Study Arms (1)

anti-CD19 CAR NK cells

EXPERIMENTAL

CD19-CAR-NK is an allogenic CD19-Targeted chimeric antigen receptor NK-cell (CAR-NK) therapy.

Biological: anti-CD19 CAR NK cells

Interventions

anti-CD19 CAR NK cells BIOLOGICAL

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.

anti-CD19 CAR NK cells

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects voluntarily participate in this clinical study and sign the Informed Consent Form (ICF).
• 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.
• 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.
• Subjects with a measurable or evaluable lesion (more than one lesion≥15mm) according to IWG criteria.
• Age≥ 18 years old and ≤ 75 years old, male or female.
• Subjects with estimated survival \> 12 weeks.
• 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).
• Absolute neutrophil count (ANC) ≥ 1.0×109/L, platelet count ≥ 50×109/L.
• ECOG performance ≤ 1.
• Left ventricular ejection fraction (LVEF) ≥50% and no clinically significant pericardial effusion.
• ≥ 4 weeks after subjects received last dose treatment (Radiotherapy, chemotherapy, monoclonal antibody therapy or other treatments).

You may not qualify if:

• 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.
• Relapsed after allogenic haemopoietic stem cell transplantation (HSCT).
• 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.
• Subjects with acquired and congenital immunodeficiency diseases.
• Subjects with grade III or IV heart failure (NYHA classification).
• History of epilepsy or other central nervous system (CNS) diseases.
• Subjects with extranodal lymphoma in Intracranial, lung, or gastrointestinal tract.
• History of other primary malignant tumors except:
• Cured non-melanoma skin cancer by surgical excision, for example basal cell carcinoma (BCC);
• Cured primary malignant tumors, such as cervical cancer, superficial bladder cancer, breast cancer.
• Systemic corticosteroids are used concomitantly within 2 weeks prior to treatment.
• Females who are pregnant, lactating, or planning a pregnancy within six months.
• Subjects who have received other clinical trial treatment within 3 months.
• Any situation judged by the investigators that may increase the risk of the subjects or interfere with the clinical trial outcome.

Sponsors & Collaborators

• Changhai Hospital: lead
• Nanjing Enricnk Biotech Co., Ltd: collaborator

Study Sites (1)

Changhai Hospital

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Jianmin Yang, Ph. D.

CONTACT

13918735105; chyangjianmin@163.com

Libing Wang, Ph.D.

CONTACT

13918735105; doctorwanglibing@126.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 6, 2023
• Study Start: March 1, 2023
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2024
• Last Updated: August 28, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)