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

Radboud University Medical Center

Status and phase: Completed; Phase 1

Conditions: Recurrent Primary Peritoneal Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma

Treatments: Biological: UCB-NK cells; Drug: Chemotherapy

Study type: Interventional

Funder types: Other

Identifiers

NCT03539406

NL60937.000.17

Details and patient eligibility

About

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.

Full 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.

Enrollment: 11 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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11 participants in 2 patient groups

NK-cells without preparative regimen

Experimental group

Description:

NK-cells without preparative regimen

Treatment:

Biological: UCB-NK cells

NK-cells with preparative regimen

Experimental group

Description:

NK-cells with preparative regimen

Treatment:

Drug: Chemotherapy

Biological: UCB-NK cells