Anti-CD19 CAR-Engineered NK Cells in the Treatment of Relapsed/Refractory B-cell Malignancies

NCT05410041 | Unknown Phase 1

• 1 other identifier: BRYY-IIT-LCYJ-2022-003
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single arm, open and multi center exploratory clinical study to observe the safety and effectiveness of CAR NK-CD19 in participants with recurrent or refractory CD19 positive B-cell malignant tumors, and preliminarily evaluate the expansion of this product in vivo and the objective remission rate after administration.

Conditions

Acute Lymphocytic Leukemia; Chronic Lymphocytic Leukemia; Non Hodgkin Lymphoma

Keywords

CAR-NK; CD19 positive; B-cell malignancy

Outcome Measures

Primary Outcomes (2)

• Safety of CAR NK-CD19 Cell

  Safety of CAR NK-CD19 will be assessed by incidence and severity of AEs and SAEs.

  Up to 3 months after cell infusion

• The overall response rate (ORR)

  Objective response rate (ORR) according to NCCN, Complete response(CR),CR with incomplete blood count recovery(CRi).

  Up to 3 months after cell infusion

Secondary Outcomes (2)

• Concentration of PK CAR positive NK cells in peripheral blood

  Up to 3 months after cell infusion

• Pharmacodynamic data in peripheral blood

  Up to 3 months after cell infusion

Other Outcomes (3)

• Duration of remission (DOR) after infusion

  From 28 to 180 days after infusion

• Progression-free survival (PFS) after infusion

  From 28 to 180 days after infusion

• Overall survival (OS) after infusion

  From 6 to 24 months after infusion

Study Arms (1)

CAR-NK-CD19 Cells

EXPERIMENTAL

After preconditioning with chemotherapy, CAR-NK-CD19 Cells will be evaluated.

Biological: CAR-NK-CD19 Cells

Interventions

CAR-NK-CD19 Cells BIOLOGICAL

CAR-NK-CD19 Cells, 1-3×10\^7 /KG, treatment follows a lymphodepletion. Drug: Fludarabine Recommendation: 25-30 mg/kg (D-5\~D-3), determined by tumor burden at baseline. Drug: Cyclophosphamide Recommendation: 250-300 mg/kg (D-5\~D-3), determined by tumor burden at baseline.

CAR-NK-CD19 Cells

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old, regardless of gender;
• Eastern Cooperative Oncology Group score 0-2;
• Participants with CD19 positive B-cell malignancies, including acute lymphocytic leukemia (all), chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL);
• Failure or recurrence of at least 2-line treatment (including immunotherapy, targeted therapy and stem cell transplantation);
• Measurable lesions with an expected survival of more than 3 months;
• The functions of liver, kidney, heart and lung meet the following requirements:
• creatinine clearance rate ≥ 60ml / min ;
• ALT (alanine transaminase, ALT) / AST (aspartate aminotransferase, AST) ≤ 2.5 times the upper normal limit;
• total bilirubin ≤ 1.5 times the upper limit of normal value, except for participants with Gilbert syndrome, the total bilirubin must be \< / = 3.0 mg / dl;
• left ventricular ejection fraction ≥ 50%, no clinically significant ECG results;
• blood oxygen saturation \> 92% in non oxygen absorption state;
• The subjects agreed to use reliable contraceptive methods for contraception within 1 year from the signing of informed consent to reinfusion. Including but not limited to: abstinence, male vasectomy, implantable progesterone contraceptives that can inhibit ovulation; Intrauterine device; Hormone releasing intrauterine device; Sexual partner sterilization; Copper IUD, correct use of proven compound hormone contraceptives that can inhibit ovulation; Progesterone contraceptives that inhibit ovulation. At the same time, the subjects should promise not to donate eggs (oocytes, oocytes) / sperm for assisted reproduction within 1 year after reinfusion;
• Voluntarily participate in clinical trials and sign informed consent.

You may not qualify if:

• Known allergic reaction, hypersensitivity, intolerance or contraindication to CAR NK-CD19 or any component of drugs that may be used in the study (including fludarabine, cyclophosphamide and tozumab), or subjects who have had severe allergic reaction in the past;
• Participants with gastrointestinal lymph nodes and / or central nervous system involvement who were judged by the researchers to be at risk by CAR NK-CD19 treatment (except those who were judged by the researchers to be more likely to benefit than risk);
• Those who have graft-versus-host response and need to use immunosuppressants; or suffering from autoimmune diseases;
• Before screening, the researchers judged that corticosteroids needed to receive a long-term therapeutic dose during the study period;
• Received the following anti-tumor treatment within the specified time before screening:
• i. Have received small molecule targeted therapy within 4 weeks or 5 half lives (whichever is longer); ii. Have received macromolecular drug treatment within 4 weeks or 2 half lives (whichever is longer); iii. Have received cytotoxic treatment or modern traditional Chinese medicine preparation with antitumor effect within 2 weeks;
• Those who have been vaccinated with live vaccine or attenuated vaccine within 4 weeks before screening; Note: it is allowed to receive inactivated virus vaccine for seasonal influenza; However, it is not allowed to receive live attenuated influenza vaccine for intranasal use;
• History of epilepsy or other central nervous system diseases;
• Other active malignant tumors in the two years before screening (except for the following cases: tumors targeted in this study, surgically removed non-melanoma skin cancer, cured cervical carcinoma in situ, local prostate cancer, low-stage bladder cancer, breast ductal carcinoma in situ, or no recurrence and no treatment of malignant tumors in the two years before randomization);
• Within 14 days before enrollment, there were active or uncontrollable infections requiring systemic treatment;
• Active hepatitis B participants; Hepatitis C virus (HCV) antibody positive; Human immunodeficiency virus (HIV) antibody positive; Syphilis antibody positive in primary screening;
• a) Participants with inactive / asymptomatic carrier, chronic or active HBV infection can be included if they meet the following conditions: HBV DNA \< 500 IU / ml (or 2500 copies / ml) at the time of screening.
• The toxicity (including peripheral neuropathy) caused by previous treatment has not fully recovered or stabilized to grade 1 (nci-ctcae V5.0) (except those that the researcher judges will not affect the patient's safe treatment, such as hair loss);
• Heart disease: there is heart failure (NYHA classification ≥ class II, Appendix 2) and serious heart disease determined by the researcher; Myocardial infarction occurred ≤ 6 months before screening; Unstable angina pectoris, severe arrhythmia judged by the researcher or coronary artery bypass grafting (CABG) occurred ≤ 3 months before screening;
• Poor control of hypertension (systolic blood pressure \> 160 mmHg and / or diastolic blood pressure \> 100 mmHg) or accompanied by hypertensive crisis or hypertensive encephalopathy;

Sponsors & Collaborators

• Beijing Boren Hospital: lead

Study Sites (1)

Beijing Boren Hospital

Beijing, Beijing Municipality, 100070, China

RECRUITING

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma

Study Officials

• Kai Hu, MD/PhD

  Beijing Boren Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kai Hu, MD/PhD

CONTACT

+8615010390336; xiaohu7079@sina.com

Study Design

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

Study Record Dates

• First Submitted: May 26, 2022
• First Posted: June 8, 2022
• Study Start: May 25, 2022
• Primary Completion: April 1, 2023
• Study Completion: May 1, 2024
• Last Updated: June 8, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)