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

NCT03539406 | Completed Phase 1 DMC

• 1 other identifier: NL60937.000.17
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment emergent adverse events

  Incidence of treatment emergent adverse events (following CTCAE criteria)

  6 months

Secondary Outcomes (5)

• in vivo lifespan of the infused UCB-NK cells

  28 days

• in vivo expansion of the infused UCB-NK cells

  28 days

• Measurement of in vitro cytolytic activity of infused NK cells

  28 days

• the effect of NK cell infusion on measurable disease

  6 months

• the effect of NK cell infusion on measurable disease

  6 months

Study Arms (2)

NK-cells without preparative regimen

EXPERIMENTAL

NK-cells without preparative regimen

Biological: UCB-NK cells

NK-cells with preparative regimen

EXPERIMENTAL

NK-cells with preparative regimen

Biological: UCB-NK cells; Drug: Chemotherapy

Interventions

UCB-NK cells BIOLOGICAL

Intraperitoneal allogeneic UCB-NK cells infusion

NK-cells with preparative regimen; NK-cells without preparative regimen

Chemotherapy DRUG

Cyclofosfamide/fludarabine treatment

NK-cells with preparative regimen

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Dutch Cancer Society: collaborator

Study Sites (1)

Radboudumc

Nijmegen, Netherlands

Location

MeSH Terms

Conditions

Ovarian Neoplasms; Fallopian Tube Neoplasms

Interventions

Drug Therapy

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 12, 2018
• First Posted: May 29, 2018
• Study Start: June 4, 2019
• Primary Completion: May 1, 2023
• Study Completion: September 1, 2023
• Last Updated: August 9, 2024

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)