Intraperitoneal Infusion of ex Vivo-cultured Allogeneic NK Cells in Recurrent Ovarian Carcinoma Patients (INTRO)

Intraperitoneal Infusion of ex Vivo-cultured Allogeneic NK Cells in Recurrent Ovarian Carcinoma Patients (a Phase I Study)

This study investigates an innovative treatment for recurrent ovarian cancer exploiting ex vivo-generated allogeneic natural killer (NK) cells with or without preceding non-myeloablative conditioning chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma
• Intervention / Treatment: Biological: UCB-NK cells; Drug: Chemotherapy

Detailed Description

This study investigates an innovative treatment for recurrent ovarian cancer exploiting ex vivo-generated allogeneic natural killer (NK) cells with or without preceding non-myeloablative conditioning chemotherapy.

This study is a phase I safety and feasibility study in a series of 12 patients who are suffering from recurrent ovarian, fallopian tube or primary peritoneal cancer. Prior to NK cell infusion, a laparoscopy is performed to place a catheter in the peritoneal cavity. The first cohort of three patients will receive an intraperitoneal infusion of allogeneic UCB-NK cells generated ex vivo from CD34+ hematopoietic progenitor cells obtained from an allogeneic UCB unit without a preparative regimen. In the second group of three patients the same UCB-NK cell dosage will be given with a preparative regimen of four days non-myeloablative immunosuppressive conditioning regimen with cyclophosphamide and fludarabine (CyFlu). If no severe toxicity is seen in these 6 patients, an extension cohort of 6 patients will be included to answer the secondary objective.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Janneke Hoogstad-van Evert, MSc.; Phone Number: 0031 24 361 3223; Email: Janneke.Hoogstad-vanEvert@radboudumc.nl
• Study Contact Backup: Name: Harry Dolstra, associate professor; Phone Number: 0031 24 361 3223; Email: harry.dolstra@radboudumc.nl

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Recruiting
    • Radboudumc
    • Contact: Harry Dolstra, associate professor
    • Principal Investigator: Harry Dolstra, associate professor

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:

• Patients suffering from their second recurrence of ovarian, fallopian tube or primary peritoneal cancer, with an elevated serum level of CA-125 on two successive time points with 28 days in between, reaching a value of more than 2 times nadir and above 35 U/ml without gastrointestinal symptoms.
• Able to undergo laparoscopic IP port placement and IP treatment administration
• Adequate organ function
• Age 18 years or older
• Age under 76 years.
• Karnofsky performance status >70% (see appendix 2)
• Life expectancy > 6 months
• At least 28 days after last anti cancer treatment, before start of preparative regimen
• Written informed consent
• Availability of a partially HLA-matched UCB unit

Exclusion Criteria:

• Patients on immunosuppressive drugs
• Patients with active infections (viral, bacterial or fungal) that requires specific therapy. Acute anti-infectious therapy must have been completed within 14 days prior to study treatment
• Laparoscopic adhesion score >4 out of 9.
• Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease (appendix 4)
• Severe pulmonary dysfunction (CTCAE III-IV) (appendix 4)
• Severe renal dysfunction (MDRD<50) (appendix 4)
• Severe hepatic dysfunction (serum bilirubin or transaminases > 3 times normal level) (appendix 4)
• Severe neurological or psychiatric disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NK-cells without preparative regimen	Biological: UCB-NK cells; Intraperitoneal allogeneic UCB-NK cells infusion
Experimental: NK-cells with preparative regimen	Biological: UCB-NK cells; Intraperitoneal allogeneic UCB-NK cells infusion; Drug: Chemotherapy; Cyclofosfamide/fludarabine treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment emergent adverse events	Incidence of treatment emergent adverse events (following CTCAE criteria)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
in vivo lifespan of the infused UCB-NK cells	determination of NK cell percentage in blood and peritoneal fluid	28 days
in vivo expansion of the infused UCB-NK cells	determination of NK cell percentage in peritoneal fluid and blood	28 days
Measurement of in vitro cytolytic activity of infused NK cells	in CFSE base killing assays a percentage of dead cells (K562 cells) will be measured.	28 days
the effect of NK cell infusion on measurable disease	CA-125 testing in blood (in E/mL)	6 months
the effect of NK cell infusion on measurable disease	CT-scan (measurement of visible leasions in cm)	6 months

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Dutch Cancer Society

Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2019
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: February 12, 2018
• First Submitted That Met QC Criteria: May 16, 2018
• First Posted (Actual): May 29, 2018

Study Record Updates

• Last Update Posted (Actual): October 28, 2022
• Last Update Submitted That Met QC Criteria: October 27, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Disease Attributes; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Carcinoma; Recurrence; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: NL60937.000.17

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