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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 (dose escalation) and Part 2 (dose expansion) | Experimental | Part 1 (dose escalation) the dose of dualCAR-NK19/70 participants receive will depend on when you join this study. Up to 3 dose levels of dualCAR-NK19/70 will be tested. About 3-6 participants will be enrolled at each dose level. The first group of participants will receive the lowest dose level of dualCAR-NK19/70. Each new group will receive a higher dose of dualCAR-NK19/70 than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of dualCAR-NK19/70 is found. Part 2 (dose expansion) Participants will receive dualCAR-NK19/70 at the recommended dose that was found in Part 1. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| dualCAR-NK19/70 cell | Drug | Given by IV (vein) |
|
| Measure | Description | Time Frame |
|---|---|---|
| incidence of dose limiting toxicity(DLTs) | To evaluate the safety,tolerabitility,and determine the recommended dosage of cord blood-derived CAR NK cells targeting CD19/CD70 | up to 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate(ORR) | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 | 6 months |
| Complete Remission Rate(CRR) | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Adverse Events | Type, frequency, and severity of adverse events,Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5 | through study completion; an average of 1 year,up to 3 years |
| Exploratory Objectives |
Inclusion Criteria:
Voluntarily participate in the study and sign the informed consent;
Age 18-75, male and female;
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.
There was at least one measurable lesion with the longest diameter ≥ 1.5cm;
Estimated life expectancy of more than 12 weeks other than primary disease;
Previously confirmed diagnosis as CD19+ or CD70+ B-NHL.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 3.
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;
Once previous autologous hematopoietic stem cell transplantation (auto-HSCT) is allowed;
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;
Either having failed or Relapsed after CAR-T therapy at 3 months of assessment;
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.
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| aibin Liang | Contact | 18601670600 | lab7182@tongji.edu.cn | |
| Ping Li | Contact | 13564181131 | lilyforever76@126.com |
| Name | Affiliation | Role |
|---|---|---|
| aibin Liang | Shanghai Tongji Hospital, Tongji University School of Medicine | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Shanghai Tongji Hospital, Tongji University School of Medicine | Recruiting | Shanghai | Shanghai Municipality | 200065 | China |
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| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| 3 months |
| Overall survival(OS) | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 | Up to 3 years |
| Duration of Response(DOR) | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 | Up to 3 years |
| progression-free survival(PFS) | To determine the anti-tumor effectivity of CB dualCAR-NK19/70 | 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. |
| Up to 3 years |
| D008232 |
| Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |