ThisCART19A for B-NHL Relapsed After Auto-CAR T
Study Details
Study Description
Brief Summary
This is a phase 1, single-center, dose selection study to evaluate the efficacy, safety, and pharmacokinetics of ThisCART19A (allogeneic CAR-T targeting CD19) in patients with Auto-CAR T relapsed B-cell non-Hodgkin's lymphoma.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This is a phase 1, single-center, dose selection study to evaluate the efficacy, safety, and pharmacokinetics of ThisCART19A in patients with Auto-CAR T relapsed B-cell non-Hodgkin's lymphoma. The study will identify a treatment regimen most likely to result in clinical efficacy while maintaining a favorable safety profile. Before initiating ThisCART19A infusion, subjects will be administered lymphodepletion chemotherapy composed of fludarabine、cyclophosphamide and VP-16. At Day 0 of the Treatment Period, subjects will receive an intravenous (IV) infusion of ThisCART19A. All subjects are monitored during the treatment period through Day 28. All subjects who receive a dose of ThisCART19A will be followed up to 2 years.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose Level 1 ThisCART19A，2×10^6 cells/kg（Single dose of Allogeneic Anti-CD19 CAR T cells will be infused） |
Drug: ThisCART19A with Dose Level 1
ThisCART19A，2×10^6 cells/kg（Single dose of Allogeneic Anti-CD19 CAR T cells will be infused）, after the lymphodepletion conditioning of fludarabine, CTX and VP-16
Other Names:
|
| Experimental: Dose Level 2 ThisCART19A，3×10^6 cells/kg（Single dose of Allogeneic Anti-CD19 CAR T cells will be infused） |
Drug: ThisCART19A with Dose Level 2
ThisCART19A，3×10^6 cells/kg（Single dose of Allogeneic Anti-CD19 CAR T cells will be infused）, after the lymphodepletion conditioning of fludarabine, CTX and VP-16
Other Names:
|
Outcome Measures
Primary Outcome Measures
- BOR [3 month]
Best Overall Response Rate
Secondary Outcome Measures
- ORR [2 year]
Objective response rate
- CR [2 year]
Complete response rate
- TTR [3 month]
Time to response
- DOR [2 year]
Duration of response
- EFS [2 year]
Event-free survival
- PFS [2 year]
Progression-free survival
- OS [2 year]
Overall survival
Eligibility Criteria
Criteria
Inclusion Criteria:
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Voluntarily sign a documented IRB-approved ICF prior to any screening procedure;
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Gender not restricted, 18 years ≤ age ≤ 75 years;
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Subjects with Auto-CAR T relapsed B-cell non-Hodgkin's lymphoma;
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Life expectancy ≥ 12 weeks at the time of enrollment;
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Eastern Cooperative Oncology Group performance status score of 0 or 1;
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At least one measurable lesion to be assessed, with any nodal lesion > 15mm in LDi (longest diameter) and any extranodal lesion > 10mm in LDi;
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Subject has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as:
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Adequate marrow function for lymphodepletion chemotherapy: 14 days before enrollment, absolute neutrophil count (ANC) ≥ 1×109/L, platelet count ≥ 30×109/L, hemoglobin ≥ 80 g/L without blood transfusion;
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Creatinine clearance ≥ 30 ml/min according to the Cockcroft-Gault formula, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 × the upper limit of normal (ULN), total bilirubin ≤ 2×ULN (Subjects with Gilbert syndrome or liver involvement may be enrolled if their total bilirubin is ≤ 3×ULN);
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Pulmonary function: Baseline oxygen saturation (SaO2) ≥ 92% on room air;
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Cardiac function：left ventricular ejection fraction (LVEF) ≥ 40% assessed by echocardiography.
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CD19-positive lymphoma confirmed on a biopsy during screening.
Exclusion Criteria:
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Allergic to preconditioning measures in the trial.
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Other malignancies apart from B-cell malignancies within 5 years prior to screening. (Subjects with cured skin squamous carcinoma, basal carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be recruited.)
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Severe active infection (Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted).
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Pulmonary embolism (PE) within 3 months prior to enrollment.
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Intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases assessed by the investigator prior to enrollment.
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Gastrointestinal involvement at risk of active bleeding.
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Massive pericardial effusion, symptomatic thoracic or abdominal effusion.
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Presence of CNS involvement (both primary and secondary) at screening confirmed by imaging or CSF testing.
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Active hepatitis B virus (serum HBV-DNA ≥ 2000 IU/mL), hepatitis C virus (HCV), human immunodeficiency virus (HIV) or active syphilis infection prior to enrollment. (Patients with HBV-DNA < 2000 IU/mL can be enrolled, but should be administered antiviral drugs such as entecavir and tenofovir with relative clinical indicators monitored simultaneously during the treatment.)
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Less than 100 days after allogeneic hematopoietic stem cell transplantation.
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Vaccinated with influenza vaccine within 2 weeks prior to lymphodepletion chemotherapy. (Patients vaccinated with SARS-COV19 vaccine or inactivated; live/non-live adjuvant vaccines can be enrolled.)
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Under treatment for graft versus host disease (GvHD). (GvHD cured subjects who had stopped immunosuppressive drugs for at least 1 month can be enrolled.)
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Female subjects who are pregnant, breastfeeding or planning for pregnancy within 1 year after CAR-T cell infusion, or male subjects whose partners are planning for pregnancy within 1 year after CAR-T cell infusion;
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Any conditions that would, in the investigator's assessment, increase risks in patients or interfere with the outcomes of the trial.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The First Affiliated Hospital of Soochow University | Suzhou | Jiangsu | China | 215000 |
Sponsors and Collaborators
- The First Affiliated Hospital of Soochow University
- Fundamenta Therapeutics, Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SZ5602