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

Sponsor

Changhai Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05673447

Collaborator

Nanjing Enricnk Biotech Co., Ltd (Other)

Enrollment

Arm

Anticipated Duration (Months)

Study Details

Study Description

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 endpionts are the overall response rates (ORR) and disease control rate (DCR).

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B Cell Lymphoma	Biological: anti-CD19 CAR NK cells	Early Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Dec 30, 2023

Anticipated Study Completion Date :

Dec 30, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

Incidence of dose limiting toxicity (DLTs) [within 4 weeks after infusion]
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.
Incidence of Treatment Emergent Adverse Events (TEAEs) [up to 48 weeks after infusion]
To characterize the safety of Anti-CD19 CAR NK Cells for Relapsed/Refractory diffuse large B cell lymphoma.

Secondary Outcome Measures

The overall response rate (ORR) [1, 3, 6 and 12 months after infusion]
To characterize the efficacy of Anti-CD19 CAR NK Cell Therapy for R/R Non-Hodgkin Lymphoma.
Disease control rate (DCR) [1, 3, 6, 12 and 12 months after infusion]
To characterize the efficacy of Anti-CD19 CAR NK Cell Therapy for R/R Non-Hodgkin Lymphoma.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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).

Exclusion Criteria:

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.