Intraperitoneal Infusion of ex Vivo-cultured Allogeneic NK Cells in Recurrent Ovarian Carcinoma Patients (INTRO)
Primary Purpose
Recurrent Ovarian Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Primary Peritoneal Carcinoma
Status
Recruiting
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
UCB-NK cells
Chemotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Recurrent Ovarian Carcinoma
Eligibility Criteria
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
Sites / Locations
- RadboudumcRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
NK-cells without preparative regimen
NK-cells with preparative regimen
Arm Description
NK-cells without preparative regimen
NK-cells with preparative regimen
Outcomes
Primary Outcome Measures
Incidence of treatment emergent adverse events
Incidence of treatment emergent adverse events (following CTCAE criteria)
Secondary Outcome Measures
in vivo lifespan of the infused UCB-NK cells
determination of NK cell percentage in blood and peritoneal fluid
in vivo expansion of the infused UCB-NK cells
determination of NK cell percentage in peritoneal fluid and blood
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.
the effect of NK cell infusion on measurable disease
CA-125 testing in blood (in E/mL)
the effect of NK cell infusion on measurable disease
CT-scan (measurement of visible leasions in cm)
Full Information
NCT ID
NCT03539406
First Posted
February 12, 2018
Last Updated
October 27, 2022
Sponsor
Radboud University Medical Center
Collaborators
Dutch Cancer Society
1. Study Identification
Unique Protocol Identification Number
NCT03539406
Brief Title
Intraperitoneal Infusion of ex Vivo-cultured Allogeneic NK Cells in Recurrent Ovarian Carcinoma Patients
Acronym
INTRO
Official Title
Intraperitoneal Infusion of ex Vivo-cultured Allogeneic NK Cells in Recurrent Ovarian Carcinoma Patients (a Phase I Study)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 4, 2019 (Actual)
Primary Completion Date
May 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Radboud University Medical Center
Collaborators
Dutch Cancer Society
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Ovarian Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Primary Peritoneal Carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
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. 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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
NK-cells without preparative regimen
Arm Type
Experimental
Arm Description
NK-cells without preparative regimen
Arm Title
NK-cells with preparative regimen
Arm Type
Experimental
Arm Description
NK-cells with preparative regimen
Intervention Type
Biological
Intervention Name(s)
UCB-NK cells
Intervention Description
Intraperitoneal allogeneic UCB-NK cells infusion
Intervention Type
Drug
Intervention Name(s)
Chemotherapy
Intervention Description
Cyclofosfamide/fludarabine treatment
Primary Outcome Measure Information:
Title
Incidence of treatment emergent adverse events
Description
Incidence of treatment emergent adverse events (following CTCAE criteria)
Time Frame
6 months
Secondary Outcome Measure Information:
Title
in vivo lifespan of the infused UCB-NK cells
Description
determination of NK cell percentage in blood and peritoneal fluid
Time Frame
28 days
Title
in vivo expansion of the infused UCB-NK cells
Description
determination of NK cell percentage in peritoneal fluid and blood
Time Frame
28 days
Title
Measurement of in vitro cytolytic activity of infused NK cells
Description
in CFSE base killing assays a percentage of dead cells (K562 cells) will be measured.
Time Frame
28 days
Title
the effect of NK cell infusion on measurable disease
Description
CA-125 testing in blood (in E/mL)
Time Frame
6 months
Title
the effect of NK cell infusion on measurable disease
Description
CT-scan (measurement of visible leasions in cm)
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Janneke Hoogstad-van Evert, MSc.
Phone
0031 24 361 3223
Email
Janneke.Hoogstad-vanEvert@radboudumc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Harry Dolstra, associate professor
Phone
0031 24 361 3223
Email
harry.dolstra@radboudumc.nl
Facility Information:
Facility Name
Radboudumc
City
Nijmegen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Harry Dolstra, associate professor
First Name & Middle Initial & Last Name & Degree
Harry Dolstra, associate professor
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Intraperitoneal Infusion of ex Vivo-cultured Allogeneic NK Cells in Recurrent Ovarian Carcinoma Patients
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