Clinical Study of the Efficacy of CD19-CAR-DNT Cells in the Treatment of Relapsed/Refractory B-cell NHL

NCT05453669 | Unknown Phase 1

• 1 other identifier: IR2022000371
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the safety and tolerability of CD19-CAR-DNT cells infusion in subjects with relapsed/refractory B-cell non-Hodgkin's Lymphoma

Conditions

B-cell Non-Hodgkin's Lymphoma

Keywords

r/r B-NHL ,Cell therapy

Outcome Measures

Primary Outcomes (3)

• DLT

  To evaluate the safety, tolerability, and determine the recommended dosage of CD19-CAR-DNT Cell Therapy for Relapsed/Refractory B-cell Non-Hodgkin Lymphoma

  Up to 28 days

• MTD

  MTD was the highest dose for DLT in ≤1/6 subjects

  Up to 28 days

• Incidence of abnormalities

  Incidence of abnormalities in AE/SAE/AESI/laboratory tests/electrocardiograms/vital signs.

  Up to 28 days

Secondary Outcomes (9)

• Pharmacokinetics (PK) indicator (Cmax)

  Up to 90 days

• Pharmacokinetics (PK) indicator (AUC)

  Up to 90 days

• Pharmacokinetics (PK) indicator (Tmax)

  Up to 90 days

• Pharmacokinetics (PK) indicator (T1/2)

  Up to 90 days

• Overall Response Rate

  Up to 2 years

Study Arms (1)

CD19-CAR-DNT cells

EXPERIMENTAL

9 patientsare planned to be enrolled in the dose-escalation trial (1×10\^6 CD19-CAR-DNT cells/kg, 3×10\^6 CD19-CAR-DNT cells/kg, 9×10\^6 CD19-CAR-DNT cells/kg) and 3 patients in the dose-expansion trial.

Biological: CD19-CAR-DNT cells

Interventions

CD19-CAR-DNT cells BIOLOGICAL

Lentiviral vector-transducted DNT cells to express anti-CD19 CAR. Prior to cellular infusion, each patient received cyclophosphamide and fludarabine lymphodepleting chemotherapy.

CD19-CAR-DNT cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily sign an ICF and expect to complete the study procedures for follow-up examinations and treatment.
• Aged 18 to 75 years (including cut-offs), regardless of gender
• A diagnosis of B-cell non-Hodgkin's lymphoma confirmed by cytology or pathological histology according to WHO 2016 criteria, including pathologically confirmed diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (TFL) and high-grade B-cell lymphoma (HGBCL).
• Relapsed/refractory B-cell non-Hodgkin's lymphoma, provided one of the following conditions is met:
• Subjects with B-cell non-Hodgkin's lymphoma who have failed at least second-line regimens (including relapse, non-remission, progression) and have received a standardised regimen of anti-CD20 monoclonal antibodies (except CD20-negative) and anthracyclines;
• Relapse after autologous haematopoietic stem cell transplantation;
• Primary resistance: induction with 2 courses of anti-CD20 monoclonal antibody-based immunochemotherapy at the time of first treatment, the best curative effect assessed as stable disease or disease progression.
• ECOG score 0 to 1.
• The presence of a measurable lesion that meets one of the following criteria:
• The long axis of the lymph node lesion exceeds 15 mm in length (the short axis is measurable);
• The long and short axes of the extralymph node lesion exceed 10 mm in length.
• Appropriate organ function, with laboratory results within 7 days prior to lymphatic clearance chemotherapy meeting the following criteria.
• Glutathione aminotransferase (AST) ≤ 3 times the upper limit of normal (ULN)
• Glutamic aminotransferase (ALT) ≤ 3 times ULN.
• Total bilirubin ≤ 1.5 times ULN, unless the subject has documented Gilbert syndrome. Subjects with Gilbert-Meulengracht syndrome with total bilirubin ≤ 3.0 times ULN and direct bilirubin ≤ 1.5 times ULN may be included.

You may not qualify if:

• Other malignancies within 5 years prior to screening, except adequately treated carcinoma in situ of the cervix, basal cell or squamous epithelial cell skin cancer, post-radical localized prostate cancer, post-radical ductal carcinoma in situ, and post-radical thyroid cancer
• Any unstable systemic disease: including but not limited to active infection (other than local infection), unstable angina, cerebrovascular accident or transient ischaemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York Heart Association class III or IV cardiac insufficiency, refractory hypertension (refractory hypertension is defined as blood pressure that has not reached standard after \>1 month of reasonably tolerable treatment with ≥3 antihypertensive drugs (including diuretics) at adequate doses based on lifestyle improvement or blood pressure that is not effectively controlled with ≥4 antihypertensive drugs), severe cardiac arrhythmias requiring pharmacologic treatment, hepatic arrhythmias, liver diseases, kidney diseases or metabolic disorders.
• Patients with B-cell non-Hodgkin's lymphoma with active central nervous system invasion.
• Patients with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titres not within the normal reference range, positive hepatitis C virus (HCV) antibody and peripheral blood HCV RNA ,positive for human immunodeficiency virus (HIV), or positive for cytomegalovirus (CMV) DNA, or positive syphilis test.
• Active or uncontrolled infections requiring systemic treatment (except simple urinary tract infections or upper respiratory tract infections).
• Subjects who are receiving systemic steroids prior to screening and who are judged by the investigator to require long-term treatment with systemic steroids during the treatment period (except for inhaled or topical use).
• Previous organ transplantation or preparation for organ transplantation (except for haematopoietic stem cell transplantation)
• Persons with acute/chronic Graft-vs-Host Disease (GvHD)
• Patients have received a haematopoietic stem cell transplant within 2 months prior to screening
• Patients have received CAR-T therapy or other gene-modified cell therapy prior to enrolment
• Active neurological autoimmune or inflammatory diseases (e.g. Guillain-Barre Syndrome (GBS), Amyotrophic lateral sclerosis (ALS)) and clinically significant active cerebrovascular disease (e.g. cerebral oedema, Posterior Reversible Encephalopathy Syndrome (PRES)). Encephalopathy Syndrome (PRES)).
• Patients with a life expectancy of less than 3 months
• Patients have been involved in other clinical studies within 3 months prior to screening.
• Patients, in the judgement of the investigator and/or clinical criteria, are contraindicated to any study procedure or have other medical conditions that may place them at unacceptable risk.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• Zhejiang Ruijiamei Biotechnologies, Co., Ltd.: collaborator

Study Sites (1)

2nd Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310009, China

RECRUITING

Related Publications (1)

• Xiao X, Liu H, Qiu X, Chen P, Li X, Wang D, Song G, Cheng Y, Yang L, Qian W. CD19-CAR-DNT cells (RJMty19) in patients with relapsed or refractory large B-cell lymphoma: a phase 1, first-in-human study. EClinicalMedicine. 2024 Feb 29;70:102516. doi: 10.1016/j.eclinm.2024.102516. eCollection 2024 Apr.

  PMID: 38444429 DERIVED

MeSH Terms

Conditions

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

Study Officials

• Wenbin Qian, MD, PhD

  2nd Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wenbin Qian, MD, PhD

CONTACT

+8613605801032; qianwb@zju.edu.cn

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: June 28, 2022
• First Posted: July 12, 2022
• Study Start: June 15, 2022
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2025
• Last Updated: July 12, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)