Clinical trial NCT05673447: The Study of Anti-CD19 CAR NK Cells in the Treatment of Relapsed/Refractory Diffuse Large B Cell Lymphoma
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 Lymphoma
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Diffuse Large B Cell Lymphoma
Keywords: B-Cell Lymphoma
CD19
CAR-NK
diffuse diffuse large B cell lymphoma
Lead sponsor: Changhai Hospital
Sponsor class: OTHER
Collaborators: name: Nanjing Enricnk Biotech Co., Ltd
First posted: 2023-01-06
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


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.

Primary outcomes:
measure: Incidence of dose limiting toxicity (DLTs)
timeFrame: within 4 weeks after infusion
measure: Incidence of Treatment Emergent Adverse Events (TEAEs)
timeFrame: up to 48 weeks after infusion
Secondary outcomes:
measure: The overall response rate (ORR)
timeFrame: 1, 3, 6 and 12 months after infusion
measure: Disease control rate (DCR)
timeFrame: 1, 3, 6, 12 and 12 months after infusion
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Changhai Hospital
Study officials:
References: