Intraperitoneal Infusion of Autologous Monocytes With Sylatron (Peginterferon Alfa-2b) and Actimmune (Interferon Gamma-1b) in Women With Recurrent or Refractory Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer

NCT02948426 | Terminated Phase 1 Results FDA Drug

• 2 other identifiers: 17001117-C-0011
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Ovarian cancer is a leading cause of cancer death in women. Monocytes are white blood cells that slow tumor growth. Interferons (IFNs) are molecules that help immune cells fight cancer. Researchers want to stimulate monocytes with IFNs. They want to test if these stimulated monocytes combined with the drugs Sylatron and Actimmune can shrink tumors and slow the progression of cancer. Objective: To test how well IFN stimulated monocytes, with Sylatron and Actimmune, kill tumor cells. Eligibility: Women ages 18 and older with certain ovarian, fallopian tube, or peritoneal cancers Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Scan Results or sample from previous biopsy Participants may have a tumor sample taken. Participants who do not have a port will have a catheter placed inside the abdominal cavity. It will be used to give the treatment. Participants will have visits for 4 days of each 28-day cycle. This includes overnight observation. Participants with ascites fluid in their abdominal cavity will have it sampled twice. Each cycle, participants will have: Blood tests Leukapheresis. Some blood is removed and put through a machine that separates out the monocytes. The rest of the blood is returned to the body. Infusion of the monocytes and study drugs Participants will have weekly phone calls in Cycle 1 and scans every 2 cycles. Participants will continue treatment until they can no longer tolerate it or their cancer gets worse. Participants will have a visit about 1 month after stopping treatment, then monthly phone calls.

Conditions

Ovarian Cancer; Primary Peritoneal Cancer; Fallopian Tube Cancer

Keywords

Immunotherapy; Adoptive Cell Therapy; Carcinomatosis; CA125

Outcome Measures

Primary Outcomes (3)

• Overall Maximum Tolerated Dose of Intraperitoneal Autologous Monocytes

  Maximum Tolerated Dose of intraperitoneal autologous monocytes.

  Cycle 1 Day 28

• Overall Maximum Tolerated Dose of Sylatron (Peginterferon Alpha-2b)

  Maximum Tolerated Dose of Sylatron (Peginterferon alpha-2b).

  Cycle 1 Day 28

• Overall Maximum Tolerated Dose of Actimmune (Interferon Gamma-1b)

  Maximum Tolerated Dose of Actimmune (Interferon gamma-1b).

  Cycle 1 Day 28

Secondary Outcomes (2)

• Number of Participants With a Response

  Participants were evaluated for response by radiographic imaging every 8 weeks, up to 80 weeks

• Time to Disease Progression

  Participants were assessed every 4 weeks by physical exam and 8 weeks by radiographic imaging for disease progression, up to 10 months.

Other Outcomes (2)

• Number of Participants With Serious or Non-serious (Any) Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Date treatment consent signed to date off study, approximately 10 months and 11 days for dose level 1,12 months and 1 day for dose level 2, 11 months and 4 days for dose level 3, and 12 months and 6 days for dose level 4.

• Number of Participants With a Grade 3 or Higher Dose-Limiting Toxicity (DLT)

  Cycle 1 Day 28

Study Arms (5)

Dose Level 1 - Sylatron 25µg (0.1 µg/ml); Actimmune 5mg (0.02µg/ml)

EXPERIMENTAL

Sylatron 25µg (0.1 µg/ml); Actimmune 5mg (0.02µg/ml). The autologous monocytes cell product in 250ml total volume of investigational combination (monocytes + ACTIMMUNE + SYLATRON) is infused via the intraperitoneal catheter over 30-60 min +/- 10 min every 28 days +/- 7 days until disease progression, limiting toxicity, intercurrent medical issues, or patient withdrawal.

Biological: Autologous Monocytes + ACTIMMUNE + SYLATRON

Dose Level 2 - Monocytes (75x10^6); Sylatron 25µg (0.1µg/ml); Actimmune 5mg (0.02µg/ml)

EXPERIMENTAL

Monocytes (75x10\^6); Sylatron 25µg (0.1µg/ml); Actimmune 5mg (0.02µg/ml). The autologous monocytes cell product in 250ml total volume of investigational combination (monocytes + ACTIMMUNE + SYLATRON) is infused via the intraperitoneal catheter over 30-60 min +/- 10 min every 28 days +/- 7 days until disease progression, limiting toxicity, intercurrent medical issues, or patient withdrawal.

Biological: Autologous Monocytes + ACTIMMUNE + SYLATRON

Dose Level 3 - Monocytes (750x10^6); Sylatron 25µg (0.1µg/ml); Actimmune 5mg (0.02µg/ml)

EXPERIMENTAL

Monocytes (750x10\^6); Sylatron 25µg (0.1µg/ml); Actimmune 5mg (0.02µg/ml). The autologous monocytes cell product in 250ml total volume of investigational combination (monocytes + ACTIMMUNE + SYLATRON) is infused via the intraperitoneal catheter over 30-60 min +/- 10 min every 28 days +/- 7 days until disease progression, limiting toxicity, intercurrent medical issues, or patient withdrawal.

Biological: Autologous Monocytes + ACTIMMUNE + SYLATRON

Dose Level 4 - Monocytes (750x10^6); Sylatron 250µg (1µg/ml); Actimmune 50mg (0.2µg/ml)

EXPERIMENTAL

Monocytes (750x10\^6); Sylatron 250µg (1µg/ml); Actimmune 50mg (0.2µg/ml). The autologous monocytes cell product in 250ml total volume of investigational combination (monocytes + ACTIMMUNE + SYLATRON) is infused via the intraperitoneal catheter over 30-60 min +/- 10 min every 28 days +/- 7 days until disease progression, limiting toxicity, intercurrent medical issues, or patient withdrawal.

Biological: Autologous Monocytes + ACTIMMUNE + SYLATRON

EX1 Dose Expansion Arm

EXPERIMENTAL

10 additional patients will be treated at the maximum tolerated dose (MTD)

Biological: Autologous Monocytes + ACTIMMUNE + SYLATRON

Interventions

Autologous Monocytes + ACTIMMUNE + SYLATRON BIOLOGICAL

The autologous monocytes cell product in 250ml total volume of investigational combination (monocytes + ACTIMMUNE + SYLATRON) is infused via the intraperitoneal catheter over 30-60 min +/- 10 min every 28 days +/- 7 days until disease progression, limiting toxicity, intercurrent medical issues, or patient withdrawal. Dosing is based on a dose escalation design including an expansion cohort at the maximum tolerated dose (MTD).

Dose Level 1 - Sylatron 25µg (0.1 µg/ml); Actimmune 5mg (0.02µg/ml); Dose Level 2 - Monocytes (75x10^6); Sylatron 25µg (0.1µg/ml); Actimmune 5mg (0.02µg/ml); Dose Level 3 - Monocytes (750x10^6); Sylatron 25µg (0.1µg/ml); Actimmune 5mg (0.02µg/ml); Dose Level 4 - Monocytes (750x10^6); Sylatron 250µg (1µg/ml); Actimmune 50mg (0.2µg/ml); EX1 Dose Expansion Arm

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed advanced metastatic or unresectable epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer that is relapsed and resistant (recurred less than 6 months after chemotherapy) or refractory (progressed on chemotherapy) to prior platinum- and taxane-based standard care systemic regimen. Or patients who are eligible for aditional platinum therapy. Histopathologic diagnosis must be confirmed in the Laboratory of Pathology (LP), National Cancer Institute (NCI).
• Patients must have measurable or evaluable disease. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as greater than or equal to 20 mm with conventional techniques or as greater than or equal to 10 mm with spiral computed tomography (CT) scan.
• Patients must be at least 4 weeks from previous therapy (chemotherapy, hormonal therapy, and radiation therapy, immunotherapy and monoclonal antibodies, alternative therapy or investigational therapeutic agents). There is no limitation on the amount of prior therapies allowed. Patients with ovarian cancer 4 weeks from previous therapy have been found to have normal monocyte function (unpublished).
• Patients who have had cranial radiation therapy need to have completed it greater than or equal to 8 weeks prior to enrollment.
• Patients are permitted to receive investigational imaging agents while on study.
• Patients who have had major surgery must be fully recovered and require a recovery period of greater than or equal to 4 weeks prior to enrolling on study.
• Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of intraperitoneal monocytes, interferon (IFN)-alpha 2 or IFN-gamma in patients \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1 (Karnofsky greater than or equal to 70%).
• Adequate renal function, defined as serum creatinine less than or equal to 1.5 X upper limit of normal (ULN), or measured creatinine clearance greater than or equal to 60 mL/min/1.73m\^2.
• Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels less than or equal to 3 X ULN and total bilirubin \< 1.5 X ULN, unless known diagnosis of Gilbert's syndrome, where bilirubin less than or equal to 5 mg/dl will be permitted. Gilbert's syndrome will be defined as elevated unconjugated bilirubin, with conjugated (direct) bilirubin within the normal range and less than 20% of the total. Total bilirubin will be permitted up to 5 mg/dl, if patients have historical readings consistent with the definition of Gilbert's syndrome prior to entering study.
• Adequate bone marrow function, defined as absolute neutrophil (ANC) greater than or equal to 1,500/mm\^3 (greater than or equal to 1.5 X106/L), platelet count greater than or equal to 75,000/mm\^3 (greater than or equal to 75 X10\^6/L), and hemoglobin greater than or equal to 8 g/dL (transfusion to obtain hemoglobin greater than or equal to 8 g/dL is allowed).
• The effects of intraperitoneal monocytes, IFN-alpha 2, and IFN-gamma on the developing human fetus are unknown. For this reason and because interferons based on animal data may cause fetal harm, women of child-bearing potential (excludes women with recurrent ovarian cancer) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately.
• Ability of subject to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• Patients cannot have previously been treated with interferons (e.g., for chronic active hepatitis).
• Lack of recovery of prior adverse events to Grade less than or equal to 1 severity (National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\] v 4.03) (except alopecia) due to therapy administered prior to the initiation of study drug dosing. Stable persistent grade 2 peripheral neuropathy may be allowed as determined on a case-bycase basis at the discretion of the Investigator as interferon has not been shown to cause or exacerbate peripheral neuropathy.
• Patients with active infection will not be eligible, but may become eligible once infection has resolved and at least 7 days have elapsed after antibiotics use was completed.
• Concomitant chronic (daily or almost daily for greater than or equal to 1 month prior) use of steroids or non-steroidal anti-steroidal anti-inflammatory drugs (NSAIDS).
• Patients with a recent history (within last 5 years) of autoimmune disease or inflammatory diseases will be excluded, because interferons may worsen these conditions. Exceptions will be allowed for vitiligo and hypothyroidism that has been stable on thyroid replacement medications for \>6 weeks.
• Impaired cardiac function or clinically significant cardiac disease including the following:
• New York Heart Association class III or IV congestive heart failure
• Myocardial infarction within the last 12 months
• Subjects known to have impaired left ventricular ejection fraction (LVEF) according to institutional standards
• History of allergic reactions attributed to compounds of chemical or biologic composition similar to interferons or other agents used in the study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations within the last 12 months that would limit compliance with study requirements. Patients with history of neuropsychiatric disorders or Major Depressive Disorder (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM 5) definition: http://dsm.psychiatryonline.org/doi/full/10.1176/appi.books.9780890425596.dsm04) requiring medical treatment will not be eligible to enroll, based on the black box warning (SYLATRON (peginterferon alfa-2b) for injection, for subcutaneous use. Merck Sharp \& Dohme Corp., a subsidiary of Merck \& Co., Inc., Whitehouse Station, NJ). Exception to this is if patients experienced transient post-partum depression that resolved and patient has been off treatment for \>10 years. Patients who are taking oral anti-depressants for normal sadness, bereavement, or grief will not be excluded.
• Pregnant women are excluded from this study because interferons based on animal data may cause fetal harm. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with interferons, breastfeeding should be discontinued if the mother is treated with intraperitoneal interferons. These potential risks may also apply to other agents used in this study.
• Patients on combination antiretroviral therapy for the treatment of HIV are ineligible because of the potential for pharmacokinetic interactions with interferons alfa and gamma.
• Patients receiving any medications or substances that are potent inhibitors or inducers of Cytochrome P450 1A2 (CYP1A2) or Cytochrome P450 2D6 (CYP2D6) are ineligible.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (9)

• Johnson CL, Green DS, Zoon KC. Human monocytes in the presence of interferons alpha2a and gamma are potent killers of serous ovarian cancer cell lines in combination with paclitaxel and carboplatin. J Interferon Cytokine Res. 2015 Jan;35(1):55-62. doi: 10.1089/jir.2014.0057. Epub 2014 Jul 28.

  PMID: 25068849 BACKGROUND

• Soderquest K, Powell N, Luci C, van Rooijen N, Hidalgo A, Geissmann F, Walzer T, Lord GM, Martin-Fontecha A. Monocytes control natural killer cell differentiation to effector phenotypes. Blood. 2011 Apr 28;117(17):4511-8. doi: 10.1182/blood-2010-10-312264. Epub 2011 Mar 9.

  PMID: 21389319 BACKGROUND

• Artis D, Spits H. The biology of innate lymphoid cells. Nature. 2015 Jan 15;517(7534):293-301. doi: 10.1038/nature14189.

  PMID: 25592534 BACKGROUND

• Phase 1 study of intraperitoneal infusion of autologous monocytes with peginterferon alfa-2b and interferon gamma-1b in women with recurrent or refractory ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. By: Nunes, Ana Tablante; Green, Daniel; Ekwede, Irene; et al. Conference: 53rd Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Location: Chicago, IL Date: JUN 02-06, 2017 Sponsor(s): Amer Soc Clin Oncol JOURNAL OF CLINICAL ONCOLOGY Volume: 35 Supplement: 15 Meeting Abstract: TPS3092 Published: MAY 20 2017

  BACKGROUND

• Production of autologous monocytes stimulated ex vivo with peg-interferon alfa 2b and interferon gamma 1b for intraperitoneal administration in phase I clinical trial. By: Duemler, Anna; Green, Daniel S.; Highfill, Steven L.; et al. Conference: ASCO-SITC Clinical Immuno-Oncology Symposium Location: San Francisco, CA Date: FEB 28-MAR 02, 2019 Sponsor(s): ASCO; SITC JOURNAL OF CLINICAL ONCOLOGY Volume: 37 Issue: 8 Supplement: S Meeting Abstract: 5 Published: MAR 10 2019

  BACKGROUND

• Green DS, Nunes AT, David-Ocampo V, Ekwede IB, Houston ND, Highfill SL, Khuu H, Stroncek DF, Steinberg SM, Zoon KC, Annunziata CM. A Phase 1 trial of autologous monocytes stimulated ex vivo with Sylatron(R) (Peginterferon alfa-2b) and Actimmune(R) (Interferon gamma-1b) for intra-peritoneal administration in recurrent ovarian cancer. J Transl Med. 2018 Jul 16;16(1):196. doi: 10.1186/s12967-018-1569-5.

  PMID: 30012146 BACKGROUND

• Green DS, Nunes AT, Tosh KW, David-Ocampo V, Fellowes VS, Ren J, Jin J, Frodigh SE, Pham C, Procter J, Tran C, Ekwede I, Khuu H, Stroncek DF, Highfill SL, Zoon KC, Annunziata CM. Production of a cellular product consisting of monocytes stimulated with Sylatron(R) (Peginterferon alfa-2b) and Actimmune(R) (Interferon gamma-1b) for human use. J Transl Med. 2019 Mar 14;17(1):82. doi: 10.1186/s12967-019-1822-6.

  PMID: 30871636 BACKGROUND

• First-in-human phase I study of intraperitoneally administered interferon-activated autologous monocytes in platinum-resistant or refractory ovarian cancer By: Cole, Christopher Browning; Annunziata, Christina M. Conference: ASCO-SITC Clinical Immuno-Oncology Symposium Location: Orlando, FL Date: FEB 06-08, 2020 Sponsor(s): Amer Soc Clin Oncol; Soc Immunotherapy Canc JOURNAL OF CLINICAL ONCOLOGY Volume: 38 Issue: 5 Supplement: S Meeting Abstract: 1 Published: FEB 10 2020

  RESULT

• Kamat K, Krishnan V, Berek JS, Dorigo O. Cell-based immunotherapy in gynecologic malignancies. Curr Opin Obstet Gynecol. 2021 Feb 1;33(1):13-18. doi: 10.1097/GCO.0000000000000676.

  PMID: 33278077 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Fallopian Tube Neoplasms; Ovarian Neoplasms; Carcinoma

Interventions

interferon gamma-1b; peginterferon alfa-2b

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Stanley Lipkowitz
• Organization: National Cancer Institute

lipkowis@navemed.nci.nih.gov

240-760-6129

Study Officials

• Stanley Lipkowitz, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 27, 2016
• First Posted: October 28, 2016
• Study Start: February 8, 2017
• Primary Completion: September 29, 2020
• Study Completion: September 29, 2020
• Last Updated: January 8, 2026
• Results First Posted: June 16, 2021

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data will be available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol Genomic Data Sharing (GDS) plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI). Genomic data are made available via the database of Genotypes and Phenotypes (dbGaP) through requests to the data custodians.

Locations

US (1)