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

Phase 1

Completed

• Conditions: Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma
• Interventions: Biological: UCB-NK cells; Drug: Chemotherapy

• Registration Number: NCT03539406
• Lead Sponsor: Radboud University Medical Center

Brief Summary

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-02-12
• Study First Submitted QC: 2018-05-16
• Study First Posted: 2018-05-29
• Study Start: 2019-06-04
• Status Verified: 2022-10
• Primary Completion: 2023-05-01
• Study Completion: 2023-09-01
• Last Update Submitted: 2024-08-07
• Last Update Posted: 2024-08-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NK-cells with preparative regimen	UCB-NK cells	NK-cells with preparative regimen
NK-cells with preparative regimen	Chemotherapy	NK-cells with preparative regimen
NK-cells without preparative regimen	UCB-NK cells	NK-cells without preparative regimen

Primary Outcome Measures

Name	Time	Method
Incidence of treatment emergent adverse events	6 months	Incidence of treatment emergent adverse events (following CTCAE criteria)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Radboudumc; 🇳🇱 Nijmegen, Netherlands