To Evaluate Safety and Efficacy of Autologous CD19 Chimeric Antigen Receptor (CAR)-T Cells in Relapsed/Refractory B- Non-Hodgkin Lymphoma (B-NHL) (CAR-T for NHL)

A Phase II Open Label Single-arm Study to Evaluate Safety and Efficacy of Autologous CD19 CAR-T Cells in Patients With Relapsed/Refractory B- Non-Hodgkin Lymphoma

A Phase II Open-Label Single-arm Study to Evaluate Safety and Efficacy of locally manufactured autologous CD19-directed CAR T-cells in Patients with Relapsed/Refractory B- Non-Hodgkin Lymphoma (B-NHL) or patients not eligible for hematopoietic stem cell transplantation (HCT)

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory B- Cell Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: CAR-T cells

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: S Fadilah Abdul Wahid Dr.; Phone Number: +60391456450; Email: sfadilah@hctm.ukm.edu.my

Study Locations

• Malaysia
  • Wilayah Persekutuan Kuala Lumpur
    • Bandar Tun Razak, Wilayah Persekutuan Kuala Lumpur, Malaysia
      • Recruiting
      • Universiti Kebangsaan Malaysia
      • Contact: S Fadilah Abdul Wahid Dr.; Phone Number: +60391456450; Email: sfadilah@hctm.ukm.edu.my
      • Principal Investigator: S Fadilah Abdul Wahid Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with histologically confirmed diagnosed with CD19 positive B cell NHL in accordance with WHO classification
• Patients who are refractory to second-line treatment or patients who relapsed after first-line treatment with no available curative options such as autologous or allogeneic haematopoietic stem cell transplantation (HSCT) or relapse within one year of autologous HSCT
• At least one measurable lesion according to revised IWG response criteria
• Age between ≥13to ≤75 years
• Adequate organ function as defined by a creatinine clearance >40 ml/min, serum alanine transaminase (ALT) < 5 times the normal value, serum bilirubin < 3 times the normal value, left ventricular ejection fraction> 45%
• Absolute neutrophil count ≥ 1500/μl, haemoglobin level ≥ 7 g/dl, platelets ≥ 50000/μl.
• Life expectancy >12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Female of childbearing age must have a negative pregnancy test and is on two effective contraception methods
• Male patients must use two effective contraception methods

Exclusion Criteria:

• Active central nervous system (CNS) lymphoma (detected by Imaging study or cerebrospinal fluid (CSF) analysis)
• Active cancer(other than NHL) or receiving cancer treatment
• Evidence of severe lung, heart (New York Heart Association class III/IV, arrhythmia, heart block, uncontrolled hypertension), liver, or renal failure or severe neurologic disorder
• Presence of active autoimmune disease requiring immunosuppressive therapy
• Human Immunodeficiency Virus (HIV) positivity
• Active Hepatitis B, and Hepatitis C infection
• Uncontrolled infection
• Pregnant/nursing female.
• Receiving autologous or allogeneic stem cell transplant within 12 weeks of enrolment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patient will infuse with autologous CD19 CAR-T cells; CD19 CAR-T cells	Drug: CAR-T cells; 2×10^6 CAR T cells/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	The ORR is the sum of patients achieving complete response (CR) and partial response (PR) at day 30, then 3 monthly up to 24 months after receiving CAR T-cells determined by the investigator following Lugano criteria in non-Hodgkin Lymphoma (NHL). Response assessment will be determined using a PET CT scan, or other relevant imaging studies and compared to the baseline (pre-CAR-T infusion) study.	From day 30, then 3 monthly until 24 months after infusion of CAR-T cells

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	Overall survival (OS) is defined as the time from the date of CAR-T cell infusion to the date of death from any cause. Patients who are still alive will be censored at the date of last contact.	OS at day 30, 6 months and one year, and 2 years following CAR-T cells infusion
Incidence of adverse events	Cumulative incidence of CAR-T cell treatment-related adverse events (AEs) graded by ASCT consensus grading criteria for cytokine release syndrome (CRS) and Immune Effector cell-associated Neurotoxicity Syndrome (ICANS) and by common terminology criteria adverse events (CTCAE) versions 5.0 for other AEs in p[articular hematotoxicity and infection.	From the time of infusion up to 24 months after infusion of CAR-T cells

Collaborators and Investigators

• Sponsor: National University of Malaysia
• Collaborators: Plutonet Sdn Bhd

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2021
• Primary Completion (Estimated): June 2, 2025
• Study Completion (Estimated): June 2, 2026

Study Registration Dates

• First Submitted: November 10, 2024
• First Submitted That Met QC Criteria: November 19, 2024
• First Posted (Estimated): November 21, 2024

Study Record Updates

• Last Update Posted (Estimated): November 21, 2024
• Last Update Submitted That Met QC Criteria: November 19, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: CD19 CAR-T cells; RR B- NHL; malaysia
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: CAR-T NHL PTS Plutonet 2021; JEP-2021-224 (Other Identifier: Research Ethics Committee Universiti Kebangsaan Malaysia (REC UKM))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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