Study of Cord Blood-derived CAR NK Cells Targeting CD19/CD70 in Refractory/Relapsed B-cell Non-Hodgkin Lymphoma

Trial Title: Study of Cord Blood-derived CAR NK Cells Targeting CD19/CD70 in Refractory/Relapsed B-cell Non-Hodgkin Lymphoma

NCT ID: NCT05842707

Condition: Refractory or Relapsed B-cell Non-Hodgkin Lymphoma

Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell

Conditions: Keywords:
B-cell Non-Hodgkin Lymphoma
CAR NK Cells Targeting CD19/CD70
Cord Blood-derived

Study type: Interventional

Study phase: Phase 1/Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: dualCAR-NK19/70 cell
Description: Given by IV (vein)
Arm group label: Part 1 (dose escalation) and Part 2 (dose expansion)

Other name: CAR-NK cell

Summary: To find the highest tolerable dose of dualCAR-NK19/70 (a type of cell therapy) that can be given to patients who have B-cell lymphoma that is relapsed or refractory.

Detailed description: Primary Objectives: --The primary objective is to determine the safety and identify the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of dualCAR-NK19/70 in patients with r/r B-cell lymphomas. Hypothesis: DualCAR-NK19/70 will be safe, well-tolerated, and effective in patients with r/r B-cell lymphomas. Secondary Objectives: --The secondary objective is to determine the efficacy in adults with r/r LBCL and FL grade 3B treated at the MTD or RP2D of dualCAR-NK19/70. Although the clinical benefit of dualCAR-NK19/70 has not yet been established, the intent of offering this treatment is to provide a possible therapeutic benefit, and thus the patient will be carefully monitored for tumor response and symptom relief in addition to safety and tolerability. Secondary endpoints include overall response rate (ORR; including CR + PR) and CR rate as defined by the Lugano Classification response criteria for malignant lymphoma, DOR, PFS, and OS. Exploratory Objectives: --The exploratory objectives are to assess the cellular kinetics and pharmacodynamic effects of dualCAR-NK19/70 and to evaluate biomarkers associated with response, resistance, and toxicity after administration of dualCAR-NK19/70 in blood and tumor samples.

Criteria for eligibility:
Criteria:
Inclusion Criteria: 1. Voluntarily participate in the study and sign the informed consent; 2. Age 18-75, male and female; 3. Histologically confirmed diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma (tFL), primary mediastinal B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), and other Indolent B-cell NHL transforming types: （A） Relapsed or Refractory DLBCL and tFL after 2 lines Immunotherapy or chemotherapy ; （B） Definition of Refractory large B cell lymphoma (SCHOLAR - 1 Research Standard) : disease progression after more than 4 courses of standard Immunotherapy or chemotherapy; Or the time of disease stabilization ≤ 6 months; Or disease progression or recurrence within 12 months after autologous hematopoietic stem cell transplantation (auto-HSCT); （C） Relapsed or Refractory MCL must be 1 line with immune chemotherapy; BTK inhibitors are resistant or intolerant as 2-line therapy; （D） Relapsed or Refractory disease after chemotherapy including rituximab and anthracycline. 4. There was at least one measurable lesion with the longest diameter ≥ 1.5cm; 5. Estimated life expectancy of more than 12 weeks other than primary disease; 6. Previously confirmed diagnosis as CD19+ or CD70+ B-NHL. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 3. 8. Adequate reserve of organ function: （A） Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST) ≤2.5 times the Upper Limit of Normal (ULN) for age; （B） A creatinine clearance (as estimated either by a direct urine collection or Cockcroft-Gault Equation) > 60mL/min; （C） Total bilirubin and alkaline phosphatase ≤1.5 times the Upper Limit of Normal (ULN) for age; （D） glomerular filtration rate > 50 ml/min （E） Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA); （F） Baseline oxygen saturation >92% on room air （G） Absolute neutrophil count > 1000/μL, Platelet count > 45,000/μL ,Hemoglobin > 80g/L; 9. Once previous autologous hematopoietic stem cell transplantation (auto-HSCT) is allowed; 10. For systemic therapy(Such as systemic chemotherapy, systemic radiotherapy and immunotherapy), at least 3 weeks，for Targeted drug therapy alone，at least 2 weeks，must have elapsed at the time of cell infusion; 11. Either having failed or Relapsed after CAR-T therapy at 3 months of assessment; 12. Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study until the follow-up period of the study. Women of childbearing potential must have a negative serum or urine pregnancy test. 13. The viral load of severe coronavirus disease 2019 (COVID-19) is undetectable per quantitative PCR and/or nucleic acid testing for two tests. Exclusion Criteria: 1. Allergic to any of the components of cell products; 2. Previous or concurrent of other type of maligant tumors; 3. Acute GvHD or generalized chronic GvHD with grade II-IV (Glucksberg standard) after previous autologous hematopoietic stem cell transplantation (auto-HSCT); Or receiving of anti-GVHD therapy; 4. Known history of systemic gene therapy within the prior 3 months; 5. Active systemic fungal, viral, or bacterial infection (except for simple urinary tract infections and bacterial pharyngitis), however, Preventive treatment is permitted; 6. Known history of infection with hepatitis B (HBsAg positive, but HBV-DNA<1000 is not excluded) or hepatitis C virus (including virus carriers), syphilis and other acquired and congenital immunodeficiency diseases, including but not limited to HIV infection; 7. Class III or IV heart failure as defined by the New York Heart Association; 8. Persisting toxicities (>grade 1, except for clinically non-significant toxicities such as alopecia, fatigue, and anorexia) due to prior trerapy; 9. Known history of active seizures or presence of seizure activities or other central nervous system disease; 10. Have evidence of central nervous system lymphoma(CNS lymphoma) on CT or MRI; 11. Breast-feeding woman; 12. Any circumstances that possibly increase the risk of subjects or interfere with study results, which judged by investigator.

Gender: All

Minimum age: 18 Years

Maximum age: 75 Years

Healthy volunteers: No

Locations:

Facility:
Name: Shanghai Tongji Hospital, Tongji University School of Medicine

Address:
City: Shanghai
Zip: 200065
Country: China

Status: Recruiting

Contact:
Last name: Aibin Liang, MD, Ph.D

Phone: 0086-021-66111019
Email: lab7182@tongji.edu.cn

Start date: January 18, 2023

Completion date: January 18, 2029

Lead sponsor:
Agency: Aibin Liang，MD，Ph.D.
Agency class: Other

Source: Shanghai Tongji Hospital, Tongji University School of Medicine

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05842707