Refractory or Relapsed B-cell Non-Hodgkin Lymphoma
Conditions
Keywords
B-cell Non-Hodgkin Lymphoma, CAR NK Cells Targeting CD19/CD70, Cord Blood-derived
Brief 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.
Interventions
DRUGdualCAR-NK19/70 cell
Given by IV (vein)
Sponsors
Aibin Liang，MD，Ph.D.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| incidence of dose limiting toxicity(DLTs) | up to 28 days | To evaluate the safety,tolerabitility,and determine the recommended dosage of cord blood-derived CAR NK cells targeting CD19/CD70 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission Rate(CRR) | 3 months | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 |
| Overall survival(OS) | Up to 3 years | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 |
| Duration of Response(DOR) | Up to 3 years | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 |
| progression-free survival(PFS) | Up to 3 years | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 |
| Objective Response Rate（ORR） | 6 months | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Events | through study completion; an average of 1 year,up to 3 years | Type, frequency, and severity of adverse events,Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5 |
| Exploratory Objectives | Up to 3 years | 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. |
Countries
China
Contacts
Primary Contactaibin Liang
Backup ContactPing Li
Outcome results
None listed