Treatment using cord blood-derived CAR NK cells for relapsed B-cell lymphoma

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

This study is testing a new cell therapy using cord blood to see if it can help people with relapsed B-cell lymphoma feel better and fight their cancer.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Tongji Hospital, Tongji University School of Medicine (Academic / other)
• Drugs / interventions: rituximab, CAR-T, chemotherapy, Immunotherapy
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT05842707 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and determine the maximum tolerated dose of dualCAR-NK19/70, a novel cell therapy targeting CD19 and CD70, in patients with refractory or relapsed B-cell non-Hodgkin lymphoma. The study will monitor participants for tumor response and symptom relief while assessing the efficacy of the treatment. Additionally, it will explore cellular kinetics and biomarkers related to treatment response and toxicity. The trial includes both primary and secondary objectives to comprehensively assess the therapeutic potential of this innovative approach.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-75 with relapsed or refractory B-cell non-Hodgkin lymphoma after multiple lines of therapy.

Not a fit: Patients with B-cell lymphoma that has not progressed after standard treatments or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat B-cell lymphomas.

How similar studies have performed: While the specific approach of dualCAR-NK19/70 is novel, similar CAR NK cell therapies have shown promise in other studies.

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Tongji Hospital, Tongji University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: aibin Liang

Conditions Refractory or Relapsed B-cell Non-Hodgkin Lymphoma; B-cell Non-Hodgkin Lymphoma; CAR NK Cells Targeting CD19/CD70; Cord Blood-derived