Clinical trial NCT03539406: Intraperitoneal Infusion of ex Vivo-cultured Allogeneic NK Cells in Recurrent Ovarian Carcinoma Patients
Official title: Intraperitoneal Infusion of ex Vivo-cultured Allogeneic NK Cells in Recurrent Ovarian Carcinoma Patients (a Phase I Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Recurrent Ovarian Carcinoma
Recurrent Fallopian Tube Carcinoma
Recurrent Primary Peritoneal Carcinoma
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Dutch Cancer Society
First posted: 2018-05-29
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence of treatment emergent adverse events
timeFrame: 6 months
Secondary outcomes:
measure: in vivo lifespan of the infused UCB-NK cells
timeFrame: 28 days
measure: in vivo expansion of the infused UCB-NK cells
timeFrame: 28 days
measure: Measurement of in vitro cytolytic activity of infused NK cells
timeFrame: 28 days
measure: the effect of NK cell infusion on measurable disease
timeFrame: 6 months
measure: the effect of NK cell infusion on measurable disease
timeFrame: 6 months
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboudumc
Study officials:
References: