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

NCT ID: NCT03539406

Last Updated: 2024-08-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-04

Study Completion Date

2023-09-01

Brief Summary

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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

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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

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Recurrent Ovarian Carcinoma Recurrent Fallopian Tube Carcinoma Recurrent Primary Peritoneal Carcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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NK-cells without preparative regimen

NK-cells without preparative regimen

Group Type EXPERIMENTAL

UCB-NK cells

Intervention Type BIOLOGICAL

Intraperitoneal allogeneic UCB-NK cells infusion

NK-cells with preparative regimen

NK-cells with preparative regimen

Group Type EXPERIMENTAL

UCB-NK cells

Intervention Type BIOLOGICAL

Intraperitoneal allogeneic UCB-NK cells infusion

Chemotherapy

Intervention Type DRUG

Cyclofosfamide/fludarabine treatment

Interventions

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UCB-NK cells

Intraperitoneal allogeneic UCB-NK cells infusion

Intervention Type BIOLOGICAL

Chemotherapy

Cyclofosfamide/fludarabine treatment

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Dutch Cancer Society

OTHER

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Radboudumc

Nijmegen, , Netherlands

Site Status

Countries

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Netherlands

Other Identifiers

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NL60937.000.17

Identifier Type: -

Identifier Source: org_study_id

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