Phase 1/2 Study Evaluating Safety and Potential Efficacy of Allocetra-OTS Via Pressurized Intra-Peritoneal Aerosol Chemotherapy as Add-on to Standard of Care Chemotherapy for Treatment of Peritoneal Metastasis

This is an open-label study to evaluate safety and potential efficacy of Allocetra-OTS in the treatment of patients with peritoneal metastasis as an add-on to the standard of care (SoC) chemotherapy.

Study Overview

• Status: Terminated
• Conditions: Peritoneal Metastases
• Intervention / Treatment: Drug: Allocetra-OTS

Detailed Description

Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) is utilized in patients with malignant dissemination to the peritoneal cavity, for the treatment of peritoneal metastasis that have a high tumor burden or are unresectable, and are unresponsive to systemic therapy.

Allocetra-OTS is an immunomodulatory cell-based therapy consisting of allogeneic peripheral blood mononuclear cells that have been modified to be engulfed by macrophages and reprogram them into their homeostatic state.

The study will evaluate the safety and potential efficacy of Allocetra-OTS in the treatment of peritoneal metastasis as an add-on to the standard of care (SoC) chemotherapy. Patients will be treated with escalating doses of Allocetra-OTS as an add-on to the chemotherapy administered via PIPAC, and in addition to systemic chemotherapy.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Israel
  • Ramat Gan, Israel
    • The Chaim Sheba Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years of age or older.
• Diagnosis of peritoneal metastasis due to any primary tumor by histopathology or cytology
• Possession of unresectable tumors (not eligible for Cytoreductive Surgery / Hyperthermic Intra-Peritoneal Chemoperfusion CRS/HIPEC).
• Adequate performance status and surgical risk
• Adequate hematopoietic, hepatic and renal function

Exclusion Criteria:

• Extraperitoneal disease.
• Bowel obstruction
• History of Liver cirrhosis with CHILD PUGH classification of B or C or signs of portal hypertension, portal vein thrombosis.
• Patient with known New York Heart Association (NYHA) class 3 or 4 symptomatic congestive heart failure, severe myocardial insufficiency, recent myocardial infarction, severe arrhythmias.
• Previous history of organ allograft or stem cell transplantation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohorts 1-2; Escalating doses of Allocetra-OTS up to 10 x 10^9 cells.	Drug: Allocetra-OTS; Allocetra-OTS is a cell-based therapy consisting of non-HLA matched allogeneic peripheral blood mononuclear cells, derived from a healthy human donor following a leukapheresis procedure, induced to an apoptotic stable state.
Experimental: Cohorts 3-4; Allocetra-OTS at the maximal tolerated dose.	Drug: Allocetra-OTS; Allocetra-OTS is a cell-based therapy consisting of non-HLA matched allogeneic peripheral blood mononuclear cells, derived from a healthy human donor following a leukapheresis procedure, induced to an apoptotic stable state.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and severity of Allocetra-OTS related adverse events (AEs) and serious adverse events (SAEs)	Number and severity of Allocetra-OTS related adverse events (AEs) and serious adverse events (SAEs) during 16-week period starting from the first administration of study treatment.	16 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Overall Response Rates (BORR)	Best Overall Response Rates (BORR) will be comprised of clinical, radiological and pathology assessments.	16 weeks
Change in specific cancer markers	Change in the specific cancer markers (CEA, CA-19-9, CA-125) from baseline to each post-PIPAC assessment.	16 weeks
Progression-free survival (PFS)	Progression-free survival (PFS) assessed based on imaging data (PET/CT)	6 months
Overall Survival (OS)	OS up to 12 months from the first administration of study treatment.	12 months
Change in quality of life	Change in quality of life according to EORTC QLQ-CR29 from screening to 16 weeks.	16 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Additional Safety Endpoint: Number and severity of related AEs and SAEs throughout 6 months from the first administration of study treatment.	Number and severity of related AEs and SAEs throughout 6 months from the first administration of study treatment.	6 months
Exploratory Endpoint: Change in macrophages and immune cells characteristics in peritoneal fluid	Change in macrophages and immune cells characteristics in peritoneal fluid and tissues from baseline up to 12 weeks.	12 weeks

Collaborators and Investigators

• Sponsor: Enlivex Therapeutics RDO Ltd.
• Investigators: Principal Investigator: Avi Nissan, MD, Department of Surgical Oncology, Sheba Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2022
• Primary Completion (Actual): March 14, 2024
• Study Completion (Actual): March 14, 2024

Study Registration Dates

• First Submitted: June 8, 2022
• First Submitted That Met QC Criteria: June 22, 2022
• First Posted (Actual): June 24, 2022

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: ENX-CL-04-001

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