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

Recurrent Ovarian Carcinoma Clinical Trial

— INTRO  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03539406
• Other study ID #: NL60937.000.17
• Status: Recruiting
• Phase: Phase 1
• Start date: June 4, 2019
• Est. completion date: October 2023

Study information

• Verified date: October 2022
• Source: Radboud University Medical Center
• Contact: Janneke Hoogstad-van Evert, MSc.
• Phone: 0031 24 361 3223
• Email: Janneke.Hoogstad-vanEvert[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: October 2023
• Est. primary completion date: May 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Ovarian Epithelial
• Ovarian Neoplasms
• Recurrence
• Recurrent Fallopian Tube Carcinoma
• Recurrent Ovarian Carcinoma
• Recurrent Primary Peritoneal Carcinoma

Intervention

Biological:
• UCB-NK cells
Intraperitoneal allogeneic UCB-NK cells infusion

Drug:
• Chemotherapy
Cyclofosfamide/fludarabine treatment

Locations

Country	Name	City	State
Netherlands	Radboudumc	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University Medical Center	Dutch Cancer Society

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment emergent adverse events	Incidence of treatment emergent adverse events (following CTCAE criteria)	6 months
Secondary	in vivo lifespan of the infused UCB-NK cells	determination of NK cell percentage in blood and peritoneal fluid	28 days
Secondary	in vivo expansion of the infused UCB-NK cells	determination of NK cell percentage in peritoneal fluid and blood	28 days
Secondary	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
Secondary	the effect of NK cell infusion on measurable disease	CA-125 testing in blood (in E/mL)	6 months
Secondary	the effect of NK cell infusion on measurable disease	CT-scan (measurement of visible leasions in cm)	6 months