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

NCT ID: NCT05673447

Last Updated: 2023-08-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-01
• Study Completion Date: 2024-12-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

anti-CD19 CAR NK cells

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

Group Type: EXPERIMENTAL

anti-CD19 CAR NK cells

Intervention Type: 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.

Interventions

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nanjing Enricnk Biotech Co., Ltd

UNKNOWN

Sponsor Role: collaborator

Changhai Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Changhai Hospital

Shanghai, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Jianmin Yang, Ph. D.

Role: CONTACT

chyangjianmin@163.com

13918735105

Libing Wang, Ph.D.

Role: CONTACT

doctorwanglibing@126.com

13918735105

Facility Contacts

Jianmin Yang, Doctor

Role: primary

yangjianmin@csco.org.cn

86-18317172636

Other Identifiers

CHEC2022-251

Identifier Type: -

Identifier Source: org_study_id