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Intraperitoneal Natural Killer Cells and INCB024360 for Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer

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ClinicalTrials.gov Identifier: NCT02118285
Recruitment Status : Completed
First Posted : April 21, 2014
Last Update Posted : December 5, 2017
Incyte Corporation
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
This is a single center phase I trial designed to determine the maximum tolerated dose (MTD) of the oral IDO inhibitor INCB024360 when administered as part of a larger regimen of intraperitoneal (IP) delivery of haploidentical donor NK cells and IL-2 after a non-myeloablative cyclophosphamide/fludarabine (Cy/Flu) preparative regimen for the treatment of recurrent ovarian, fallopian tube, and primary peritoneal cancer.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Fallopian Tube Carcinoma Primary Peritoneal Carcinoma Drug: Fludarabine Drug: Cyclophosphamide Biological: NK cells Biological: IL-2 Drug: INCB024360 Phase 1

Detailed Description:

Haploidentical donor NK cells and the 1st dose of IL-2 are infused intraperitoneally (IP) after a non-myeloablative preparative regimen of cyclophosphamide and fludarabine. IP IL-2 continues three times a week for 5 additional doses. INCB024360, at the assigned dose, begins 2 days before the NK cell infusion (on day -2) and continues twice daily for 90 days.

Follow-up for disease response and survival is for 1 year from the NK cell infusion with the possibility of re-treatment for patients who experience at least a clinical benefit for a minimum of 6 months prior to disease progression.

The MTD of INCB024360 will be determined using the continual reassessment method (CRM). The 1st 2 patients will be enrolled at dose level 1 (50 mg bid) of INCB024360. Each new cohort of 2 patients will be sequentially assigned to most appropriate dose by the study statistician based on the updated toxicity profile. Up to 4 dose levels of INCB024360 will be tested (50, 100, 200, and 300 mg bid) with a dose level -1 (25 mg bid) used in the event that 50 mg bid proves to be too toxic. The MTD will be identified when the total sample size of 20 patients is exhausted.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Indoleamine-2,3-dioxygenase (IDO) Inhibition With INCB024360 and Intraperitoneal Delivery of Allogeneic Natural Killer Cells for Women With Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer
Actual Study Start Date : July 28, 2014
Actual Primary Completion Date : November 12, 2015
Actual Study Completion Date : November 12, 2015

Arm Intervention/treatment
Experimental: Treatment
Haploidentical donor NK cells and IL-2 are infused intraperitoneally (IP) after a non-myeloablative preparative regimen of cyclophosphamide and fludarabine. INCB024360, at the assigned dose, begins 2 days before the NK cell infusion and continues twice daily for 90 days.
Drug: Fludarabine
Fludarabine 25 mg/m^2 IV on days -6 through -2 from NK cell infusion
Other Name: Fludara

Drug: Cyclophosphamide
Cyclophosphamide 30 mg/kg IV on days -5 and -4 from NK cell infusion
Other Names:
  • Endoxan
  • Cytoxan
  • Neosar
  • Procytox
  • Revimmune

Biological: NK cells
CD3-/CD19- selected NK cells administered by intraperitoneal (IP) infusion on day 0
Other Name: Natural Killer Cells

Biological: IL-2
IL-2 at 6 million units/dose IP 3 times a week x 6 doses with the 1st dose given immediately after the NK cell infusion
Other Name: Interleukin 2

Drug: INCB024360
INCB024360 at assigned dose by mouth twice a day begin day -2 and continue for 90 days (+/- 3 days)

Primary Outcome Measures :
  1. Maximum tolerated dose of INCB024360 [ Time Frame: 90 days ]
    To determine the maximum tolerated dose (MTD) of INCB024360 when administered with intraperitoneal haploidentical donor NK cells/IL-2 after a nonmyeloablative cyclophosphamide/fludarabine (Cy/Flu) preparative regimen in patients with recurrent ovarian, fallopian tube, and primary peritoneal cancer

Secondary Outcome Measures :
  1. Initial tumor response [ Time Frame: 90 days ]
    The proportion of patients with initial tumor response (CR or PR)

  2. Duration of tumor response [ Time Frame: 1 year ]
    Duration of tumor response

  3. Progression-free survival [ Time Frame: 5 years ]
    Average time to progression.

  4. Overall survival [ Time Frame: 5 years ]
    Average length of survival after treatment

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Diagnosis of recurrent epithelial ovarian cancer, fallopian tube, or primary peritoneal cancer that has failed or progressed after at least 1 prior salvage chemotherapy regimen directed at recurrent/metastatic disease.
  • Measurable disease per disease specific RECIST version 1.1- patients with bone as their only site of disease will not be eligible
  • If history of brain metastases must be stable for at least 3 months after treatment - A brain CT scan will only be required in subjects with known brain metastases at the time of enrollment or in subjects with clinical signs or symptoms suggestive of brain metastases.
  • Available related HLA-haploidentical NK cell donor by at least Class I serologic typing at the A&B locus
  • Age 18 years or older
  • GOG Performance Status ≥ 2 - refer to appendix III
  • Adequate organ function as determined by the following criteria within 14 days of the start of the preparative regimen, unless otherwise noted:

    • Bone marrow: platelets ≥ 80,000 x 109/L and hemoglobin ≥ 9 g/dL, unsupported by transfusions; absolute neutrophil count (ANC) ≥ 1000 x 109/L, unsupported by G-CSF or granulocytes
    • Renal function: estimated glomerular filtration rate (GFR) of ≥ 50 ml/min (based on the Fairview Laboratories formula at time of screening)
    • Liver function: total bilirubin < 1.5 times upper limit of institutional normal; AST, ALT, and alkaline phosphatase < 3 times upper limit of institutional normal
    • Cardiac: Left ventricular ejection fraction > 40% (within 28 days of treatment start)
    • Pulmonary function: > 50% corrected DLCO and FEV1, if presence of pleural effusion due to metastatic disease > 40% corrected DLCO and FEV1 is acceptable (within 28 days of treatment start)
  • Able to be off prednisone or other immunosuppressive medications other than that prescribed per protocol for at least 3 days prior to Day 0
  • At least 14 days must lapse between last prior anti-cancer treatment and 1st day of preparative regimen
  • Not pregnant or lactating - The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. Participants of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy and agree to use adequate birth control during study treatment.
  • Able to tolerate intraperitoneal (IP) port placement and IP treatment administration in the opinion of the enrolling investigator
  • Voluntary written consent

Exclusion Criteria:

  • Active infection - must be afebrile and off antibiotics
  • Receiving monoamine oxidase inhibitors (MAOI)s or drug which as significant MAOI activity (meperidine, linezolid, methylene blue) within 21 days of 1st dose of fludarabine
  • Requiring potent CYP3A4 inducers or inhibitors
  • Have ever had Serotonin Syndrome after receiving one or more serotonergic drugs
  • Prior therapy with anti-CTLA-4 antibody, anti PD-1, or an experimental immune system-targeted therapy
  • Use of any UGT1A9 inhibitor including: diclofenac, imipramine, ketoconazole, mefenamic acid, and probenecid from screening through follow-up period.
  • Undergone an organ transplant(s) including allogeneic stem cell or bone marrow transplants.
  • Unstable cardiovascular disease (eg, uncontrolled hypertension, peripheral vascular disease, congestive heart failure, cardiac arrhythmia, or acute coronary syndrome) within 6 months of starting study treatment.
  • Any gastrointestinal condition causing malabsorption or obstruction (eg, celiac sprue, gastric bypass surgery, strictures, adhesions, history of small bowel resection, blind loop syndrome). Unable or unwilling to swallow tablets BID.
  • Active autoimmune process (eg rheumatoid arthritis, moderate or severe psoriasis, multiple sclerosis, inflammatory bowel disease, etc.) or who have been receiving therapy for an autoimmune or inflammatory disease. Vitiligo, thyroiditis, or eczema is permitted if patient is otherwise eligible
  • Known HIV-positivity
  • History of hepatitis or positive serology as follows:

    • Hepatitis B (HepB) screening testing required:
  • HepB SAg (hepatitis B surface antigen);
  • Anti-HepB SAg (antibody against hepatitis B surface antigen);
  • Anti-Hepatitis B core IgG (antibody against hepatitis B core antigen).
  • Hepatitis B core IgM antibody

    • Hepatitis C screening testing required:
  • HCV-antibody (antibody against hepatitis C virus);
  • HCV-RNA (serum test for circulating virus, based on detecting RNA)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02118285

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United States, Minnesota
University of Minnesota Masonic Cancer Center
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Incyte Corporation
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Principal Investigator: Melissa Geller, MD University of Minnesota
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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT02118285    
Other Study ID Numbers: 2012LS101
MT2013-11 ( Other Identifier: University of Minnesota Blood and Marrow Transplant Program )
First Posted: April 21, 2014    Key Record Dates
Last Update Posted: December 5, 2017
Last Verified: December 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Masonic Cancer Center, University of Minnesota:
Ovarian cancer
Fallopian cancer
Primary peritoneal cancer
Additional relevant MeSH terms:
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Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Neoplasms by Site
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents