Recurrent Fallopian Tube Carcinoma, Recurrent Ovarian Carcinoma, Recurrent Primary Peritoneal Carcinoma
Conditions
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.
Interventions
BIOLOGICALUCB-NK cells
Intraperitoneal allogeneic UCB-NK cells infusion
DRUGChemotherapy
Cyclofosfamide/fludarabine treatment
Sponsors
Dutch Cancer Society
Radboud University Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment emergent adverse events | 6 months | Incidence of treatment emergent adverse events (following CTCAE criteria) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| in vivo lifespan of the infused UCB-NK cells | 28 days | determination of NK cell percentage in blood and peritoneal fluid |
| in vivo expansion of the infused UCB-NK cells | 28 days | determination of NK cell percentage in peritoneal fluid and blood |
| 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 | CA-125 testing in blood (in E/mL) |
Countries
Netherlands
Outcome results
None listed