Recurrent Ovarian CarcinomaPhase 1INTRONCT03539406
Intraperitoneal Infusion of ex Vivo-cultured Allogeneic NK Cells in Recurrent Ovarian Carcinoma Patients
A Phase 1 study testing UCB-NK cells and Chemotherapy in people with Recurrent Ovarian Carcinoma and Recurrent Fallopian Tube Carcinoma, run by Radboud University Medical Center at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Recurrent Ovarian Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Primary Peritoneal Carcinoma
- What is being tested?
- UCB-NK cells and Chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteNetherlands
- Study dates
- 4 Jun 2019to 1 Sep 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Show all 10Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Recurrent Ovarian Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Primary Peritoneal Carcinoma
- Being tested
- UCB-NK cells, Chemotherapy
- Medical subject headings
- Ovarian Neoplasms, Fallopian Tube Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UCB-NK cellsBiological
Intraperitoneal allogeneic UCB-NK cells infusion
ChemotherapyDrug
Cyclofosfamide/fludarabine treatment
| Study group | Role | What they receive |
|---|---|---|
| NK-cells without preparative regimen | Experimental | NK-cells without preparative regimen Receives: Biological: UCB-NK cells |
| NK-cells with preparative regimen | Experimental | NK-cells with preparative regimen Receives: Biological: UCB-NK cells; Drug: Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment emergent adverse events
Incidence of treatment emergent adverse events (following CTCAE criteria)
Measured: 6 months
Secondary outcomes (5)
in vivo lifespan of the infused UCB-NK cells
determination of NK cell percentage in blood and peritoneal fluid
Measured: 28 days
in vivo expansion of the infused UCB-NK cells
determination of NK cell percentage in peritoneal fluid and blood
Measured: 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.
Measured: 28 days
the effect of NK cell infusion on measurable disease
CA-125 testing in blood (in E/mL)
Measured: 6 months
the effect of NK cell infusion on measurable disease
CT-scan (measurement of visible leasions in cm)
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2018
- Study start4 Jun 2019
- Primary completion1 May 2023
- Study completion1 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Ovarian CarcinomaStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Dutch Cancer Society
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03539406
- Sponsor's protocol ID
- NL60937.000.17
- Acronym
- INTRO
- Status last verified
- Oct 2022
- First submitted
- 12 Feb 2018
- Last updated
- 9 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hoogstad-van Evert JS, de Jonge PKJD, Zusterzeel PLM, Hobo W, van der Waart AB, Fredrix H, Janssen L, Wuts M, Bosmans L, Spijkers E, Djojoatmo M, Rodriguez VC, de Goede AL, van der Reijden B, van der Meer A, Schaap N, Bekkers R, Jansen JH, Ottevanger N, Dolstra H. Intraperitoneal infusion of stem cell-derived natural killer cells in recurrent epithelial ovarian cancer patients: Results of the phase 1 INTRO-01 trial. Gynecol Oncol. 2026 Jan;204:91-99. doi: 10.1016/j.ygyno.2025.11.006. Epub 2025 Nov 24.
PubMed 41289795
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intraperitoneal Infusion of ex Vivo-cultured Allogeneic NK Cells in Recurrent Ovarian Carcinoma Patients (a Phase I Study)
- ClinicalTrials.gov ID
- NCT03539406
- Acronym / sponsor ID
- INTRO / NL60937.000.17
- Conditions
- Recurrent Ovarian Carcinoma, Recurrent Fallopian Tube Carcinoma, Recurrent Primary Peritoneal Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Dutch Cancer Society
- Study start
- 4 Jun 2019 (actual)
- Primary completion
- 1 May 2023 (actual)
- Study completion
- 1 Sep 2023 (actual)
- First posted
- 29 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| NK-cells without preparative regimen | Experimental | Biological: UCB-NK cellsNK-cells without preparative regimen |
| NK-cells with preparative regimen | Experimental | Biological: UCB-NK cells, Drug: ChemotherapyNK-cells with preparative regimen |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UCB-NK cellsIntraperitoneal allogeneic UCB-NK cells infusion | Biological | NK-cells with preparative regimen, NK-cells without preparative regimen |
| ChemotherapyCyclofosfamide/fludarabine treatment | Drug | NK-cells with preparative regimen |
Primary outcome
Incidence of treatment emergent adverse events
Time frame: 6 months
Incidence of treatment emergent adverse events (following CTCAE criteria)
5 secondary outcomes
in vivo lifespan of the infused UCB-NK cells
Time frame: 28 days
in vivo expansion of the infused UCB-NK cells
Time frame: 28 days
Measurement of in vitro cytolytic activity of infused NK cells
Time frame: 28 days
the effect of NK cell infusion on measurable disease
Time frame: 6 months
the effect of NK cell infusion on measurable disease
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
- Derived from this study: PubMed 41289795Hoogstad-van Evert JS, de Jonge PKJD, Zusterzeel PLM, Hobo W, van der Waart AB, Fredrix H, Janssen L, Wuts M, Bosmans L, Spijkers E, Djojoatmo M, Rodriguez VC, de Goede AL, van der Reijden B, van der Meer A, Schaap N, Bekkers R, Jansen JH, Ottevanger N, Dolstra H. Intraperitoneal infusion of stem cell-derived natural killer cells in recurrent epithelial ovarian cancer patients: Results of the phase 1 INTRO-01 trial. Gynecol Oncol. 2026 Jan;204:91-99. doi: 10.1016/j.ygyno.2025.11.006. Epub 2025 Nov 24.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing UCB-NK cells and Chemotherapy in people with Recurrent Ovarian Carcinoma and Recurrent Fallopian Tube Carcinoma, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment emergent adverse events (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03539406, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Aug 2024.