NCT02118285

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
2

participants targeted

Target at below P25 for phase_1 ovarian-cancer

Timeline
Completed

Started Jul 2014

Shorter than P25 for phase_1 ovarian-cancer

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 26, 2014

Completed
26 days until next milestone

First Posted

Study publicly available on registry

April 21, 2014

Completed
3 months until next milestone

Study Start

First participant enrolled

July 28, 2014

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 12, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 12, 2015

Completed
Last Updated

December 5, 2017

Status Verified

December 1, 2017

Enrollment Period

1.3 years

First QC Date

March 26, 2014

Last Update Submit

December 3, 2017

Conditions

Ovarian CancerFallopian Tube CarcinomaPrimary Peritoneal Carcinoma

Keywords

Ovarian cancerFallopian cancerPrimary peritoneal cancer

Outcome Measures

Primary Outcomes (1)

  • Maximum tolerated dose of INCB024360

    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

    90 days

Secondary Outcomes (4)

  • Initial tumor response

    90 days

  • Duration of tumor response

    1 year

  • Progression-free survival

    5 years

  • Overall survival

    5 years

Study Arms (1)

Treatment

EXPERIMENTAL

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: FludarabineDrug: CyclophosphamideBiological: NK cellsBiological: IL-2Drug: INCB024360

Interventions

FludarabineDRUG

Fludarabine 25 mg/m\^2 IV on days -6 through -2 from NK cell infusion

Also known as: Fludara
Treatment
CyclophosphamideDRUG

Cyclophosphamide 30 mg/kg IV on days -5 and -4 from NK cell infusion

Also known as: Endoxan, Cytoxan, Neosar, Procytox, Revimmune
Treatment
NK cellsBIOLOGICAL

CD3-/CD19- selected NK cells administered by intraperitoneal (IP) infusion on day 0

Also known as: Natural Killer Cells
Treatment
IL-2BIOLOGICAL

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

Also known as: Interleukin 2
Treatment
INCB024360DRUG

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

Treatment

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • +2 more criteria

You may not qualify if:

  • 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);
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Minnesota Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Ovarian NeoplasmsFallopian Tube Neoplasms

Interventions

fludarabinefludarabine phosphateCyclophosphamideIL32 protein, humanInterleukin-2epacadostat

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersFallopian Tube Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsInterleukinsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsLymphokinesProteinsBiological Factors

Study Officials

  • Melissa Geller, MD

    University of Minnesota

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 26, 2014

First Posted

April 21, 2014

Study Start

July 28, 2014

Primary Completion

November 12, 2015

Study Completion

November 12, 2015

Last Updated

December 5, 2017

Record last verified: 2017-12

Locations

US(1)