ThisCART19A for B-NHL Relapsed After Auto-CAR T

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

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.

Study Overview

• Status: Recruiting
• Conditions: B Cell Lymphoma; CAR; Relapsed Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: ThisCART19A with Dose Level 1; Drug: ThisCART19A with Dose Level 2

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 Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jia Chen, M.D., Ph.D.; Phone Number: +86-512-67781856; Email: drchenjia@163.com
• Study Contact Backup: Name: Jun Li, Ph.D.; Phone Number: +86-18662604088; Email: jli@ctigen.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215000
      • Recruiting
      • The First Affiliated Hospital of Soochow University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Voluntarily sign a documented IRB-approved ICF prior to any screening procedure;
2. Gender not restricted, 18 years ≤ age ≤ 75 years;
3. Subjects with Auto-CAR T relapsed B-cell non-Hodgkin's lymphoma;
4. Life expectancy ≥ 12 weeks at the time of enrollment;
5. Eastern Cooperative Oncology Group performance status score of 0 or 1;
6. At least one measurable lesion to be assessed, with any nodal lesion > 15mm in LDi (longest diameter) and any extranodal lesion > 10mm in LDi;

7. Subject has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function defined as:

   1. 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;
   2. 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);
   3. Pulmonary function: Baseline oxygen saturation (SaO2) ≥ 92% on room air;
   4. Cardiac function：left ventricular ejection fraction (LVEF) ≥ 40% assessed by echocardiography.
8. CD19-positive lymphoma confirmed on a biopsy during screening.

Exclusion Criteria:

1. Allergic to preconditioning measures in the trial.
2. 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.)
3. Severe active infection (Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted).
4. Pulmonary embolism (PE) within 3 months prior to enrollment.
5. Intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases assessed by the investigator prior to enrollment.
6. Gastrointestinal involvement at risk of active bleeding.
7. Massive pericardial effusion, symptomatic thoracic or abdominal effusion.
8. Presence of CNS involvement (both primary and secondary) at screening confirmed by imaging or CSF testing.
9. 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.)
10. Less than 100 days after allogeneic hematopoietic stem cell transplantation.
11. 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.)
12. Under treatment for graft versus host disease (GvHD). (GvHD cured subjects who had stopped immunosuppressive drugs for at least 1 month can be enrolled.)
13. 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;
14. Any conditions that would, in the investigator's assessment, increase risks in patients or interfere with the outcomes of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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: ThisCART19A with 2×10^6 cells/kg
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: ThisCART19A with 3×10^6 cells/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BOR	Best Overall Response Rate	3 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DOR	Duration of response	2 year
OS	Overall survival	2 year
ORR	Objective response rate	2 year
CR	Complete response rate	2 year
TTR	Time to response	3 month
EFS	Event-free survival	2 year
PFS	Progression-free survival	2 year

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Collaborators: Fundamenta Therapeutics, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Anticipated): November 30, 2025
• Study Completion (Anticipated): November 30, 2025

Study Registration Dates

• First Submitted: December 27, 2022
• First Submitted That Met QC Criteria: January 18, 2023
• First Posted (Actual): January 19, 2023

Study Record Updates

• Last Update Posted (Actual): January 19, 2023
• Last Update Submitted That Met QC Criteria: January 18, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Universal CAR-T
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: SZ5602

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No