Autologous Natural Killer Cell Therapy for Hepatocellular Carcinoma

A Phase I Study of Autologous Natural Killer Cell Therapy for Hepatocellular Carcinoma

This study represents a phase I clinical trial that utilizes natural killer (NK) cell therapy for patients diagnosed with liver cancer, specifically those classified as Child-Pugh A and falling within the Barcelona Clinic Liver Cancer (BCLC) stages B or C. The expected results include determining the suitable treatment dosage, identifying any resulting side effects, and calculating the average duration of progression-free survival. The target group for the study consists of all individuals diagnosed with liver cancer. At the same time, the practical sample consists of those who received medical care for liver cancer at Cipto Mangunkusumo Hospital (RSCM) between May and December 2022. The chosen research sample comprises liver cancer patients who fulfill the predetermined participation criteria. The necessary sample size for discerning appropriate treatment dosages and the occurrence rate of potential side effects shall consist of 2-3 liver cancer patients who are administered autologous NK cells. The process for isolating these NK cells adheres to the guidelines established by Miltenyi Biotec.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Autologous Natural Killer Cell Therapy; Device: Clinimacs Plus

• Study Type: Interventional
• Enrollment (Estimated): 3
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Ardhi Rahman Ahani, MD; Phone Number: +62 87870171876; Email: ardhi.ahani@gmail.com
• Study Contact Backup: Name: Firshan Makbul, MD; Phone Number: +62 81242625535; Email: makbulfirshan@gmail.com

Study Locations

• Indonesia
  • Jakarta
    • Jakarta Pusat, Jakarta, Indonesia, 10430
      • Recruiting
      • Cipto Mangunkusumo General Hospital
      • Contact: Ardhi Rahman Ahani, MD; Phone Number: +62 87870171876
      • Contact: Cosphiadi Irawan, MD, PhD
      • Principal Investigator: Cosphiadi Irawan, MD, PhD
      • Sub-Investigator: Ardhi Rahman Ahani, MD
      • Sub-Investigator: Chyntia Olivia Maurine Jasirwan, MD, PhD
      • Sub-Investigator: Radiana Dhewayani Antarianto, MD, MBiomed, PhD
      • Sub-Investigator: Isabella Kurnia Liem, MD, MBiomed, PhD
      • Sub-Investigator: Iqbal Fasha, MBiomed

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged 20-60 years old
• Patients with Hepatocellular Carcinoma (HCC) staged as BCLC B and C
• Karnofsky Performance Status (KPS) score ≥ 70
• Expected patient survival of more than three months
• The following parameters are within the normal range:

Platelet count ≥ 80,000/µL White blood cell count ≥ 3000/µL Neutrophil count ≥ 2000 Hemoglobin ≥ 9 mg/dL International Normalized Ratio (INR) 0.8-1.5 Adequate liver function (bilirubin < 2, SGOT and SGPT < 60 U/L) Adequate kidney function (serum creatinine < 1.3, serum urea < 10)

Exclusion Criteria:

• Refusing to participate in the study
• Afflicted by other malignancies, whether non-HCC liver or other malignancies
• Patients are affected by other conditions such as hypertension, severe coronary disease, myelosuppression, respiratory disorders, and acute or chronic infections
• Patients who have previously undergone transplantation and received other stem cell therapies

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: Autologous Natural Killer Cell; Dosage Form: Autologous Natural Killer (NK) Cells. These cells will be harvested from the patient's body and infused back into the patient. Dosage: The specific dose quantity will be determined based on the patient's medical condition and response to the treatment. Customized dosages will be calculated for each individual. Frequency: The treatment will be given through an intravenous method. Duration: The length of the treatment will vary depending on how the patient responds and their medical assessment. It may take several weeks to evaluate its effectiveness and potential impacts thoroughly.

Drug: Autologous Natural Killer Cell Therapy; The therapy will be administered intravenously; Device: Clinimacs Plus; The CliniMACS Plus device is an automated cell separation tool that uses MACS Technology. It incorporates a flexible system designed for isolating clinically labeled cells using MicroBeads.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Optimal treatment dosage	To evaluate the safety of autologous NK cell infusion and discover dose-limiting toxicities (DLT). This evaluation will determine the recommended dosage for the next trial phase.	Start of infusion of Autologous NK cells (Day 0) until up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Shrinkage	CT scans will measure tumor size at baseline and specific post-infusion times. Tumor response will be assessed using mRECIST criteria.	Up to 6 months
Immunological Responses	Flow cytometry will evaluate infused NK cells' biomarkers, such as CD45 and CD56, that persist in peripheral blood. These biomarkers will be evaluated pre- and post-infusion.	Up to 6 months
Hematology Profile	Changes of Complete Blood Count (CBC), Differential Blood Count, Coagulation Profile, Mean Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amio Transferase (AST) from baseline at each assessment time point	Start of infusion of Autologous NK cells (Day 0) until up to 6 months
Progression-free survival	This metric indicates the period during which a patient's condition shows no signs of progressing or deteriorating subsequent to the administration of autologous natural killer (NK) cell therapy	Start of infusion of Autologous NK cells (Day 0) until progressive disease or death, whichever comes first, up to 2 years

Collaborators and Investigators

• Sponsor: Dr Cipto Mangunkusumo General Hospital
• Investigators: Principal Investigator: Cosphiadi Irawan, MD, PhD, Cipto Mangunkusumo Hospital/Faculty of Medicine, Universitas Indonesia

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 1, 2023
• First Submitted That Met QC Criteria: September 13, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 24, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Immunotherapy; Natural Killer Cell
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: 22080996

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: Yes
• product manufactured in and exported from the U.S.: Yes