NCT05691153RecruitingPhase 1
A Single-center, Dose Selection Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Allogeneic CAR-T Targeting CD19 in Patients With Auto-CAR T Relapsed B-cell Non-Hodgkin's Lymphoma
The First Affiliated Hospital of Soochow University1 site in 1 country20 target enrollmentStarted: December 1, 2022Last updated:
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- BOR
Study Overview
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.
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
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntarily sign a documented IRB-approved ICF prior to any screening procedure;
- •Gender not restricted, 18 years ≤ age ≤ 75 years;
- •Subjects with Auto-CAR T relapsed B-cell non-Hodgkin's lymphoma;
- •Life expectancy ≥ 12 weeks at the time of enrollment;
- •Eastern Cooperative Oncology Group performance status score of 0 or 1;
- •At least one measurable lesion to be assessed, with any nodal lesion > 15mm in LDi (longest diameter) and any extranodal lesion > 10mm in LDi;
- •Subject has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as:
- •Adequate marrow function for lymphodepletion chemotherapy: 14 days before enrollment, absolute neutrophil count (ANC) ≥ 1×10^9/L, platelet count ≥ 30×10^9/L, hemoglobin ≥ 80 g/L without blood transfusion;
- •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);
- •Pulmonary function: Baseline oxygen saturation (SaO2) ≥ 92% on room air;
- •Cardiac function：left ventricular ejection fraction (LVEF) ≥ 40% assessed by echocardiography.
- •CD19-positive lymphoma confirmed on a biopsy during screening.
Exclusion Criteria
- •Allergic to preconditioning measures in the trial.
- •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.)
- •Severe active infection (Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted).
- •Pulmonary embolism (PE) within 3 months prior to enrollment.
- •Intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases assessed by the investigator prior to enrollment.
- •Gastrointestinal involvement at risk of active bleeding.
- •Massive pericardial effusion, symptomatic thoracic or abdominal effusion.
- •Presence of CNS involvement (both primary and secondary) at screening confirmed by imaging or CSF testing.
- •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.)
- •Less than 100 days after allogeneic hematopoietic stem cell transplantation.
- •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.)
- •Under treatment for graft versus host disease (GvHD). (GvHD cured subjects who had stopped immunosuppressive drugs for at least 1 month can be enrolled.)
- •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;
- •Any conditions that would, in the investigator's assessment, increase risks in patients or interfere with the outcomes of the trial.
Arms & Interventions
Dose Level 1
Experimental
ThisCART19A，2×10^6 cells/kg（Single dose of Allogeneic Anti-CD19 CAR T cells will be infused）
Intervention: ThisCART19A with Dose Level 1 (Drug)
Dose Level 2
Experimental
ThisCART19A，3×10^6 cells/kg（Single dose of Allogeneic Anti-CD19 CAR T cells will be infused）
Intervention: ThisCART19A with Dose Level 2 (Drug)
Outcomes
Primary Outcomes
BOR
Time Frame: 3 month
Best Overall Response Rate
Secondary Outcomes
- DOR(2 year)
- EFS(2 year)
- PFS(2 year)
- OS(2 year)
- ORR(2 year)
- CR(2 year)
- TTR(3 month)
Investigators
Study Sites (1)
Loading locations...
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