Fallopian Tube CancerPhase 1NCT02948426
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
A Phase 1 study testing Autologous Monocytes + ACTIMMUNE + SYLATRON in people with Fallopian Tube Cancer and Ovarian Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Fallopian Tube Cancer, Ovarian Cancer, Primary Peritoneal Cancer
- What is being tested?
- Autologous Monocytes + ACTIMMUNE + SYLATRON
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Feb 2017to 29 Sep 2020
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- Patients who are receiving any other investigational agents (with exception of imaging agents as indicated above in the inclusion criteria).
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Phase 1 Study of 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
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:
Read more
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.
Read the detailed description
Background:
- Monocytes can differentiate into classic M1 (classically activated) macrophages inhibiting tumor proliferation and promoting natural killer (NK) cell differentiation.
- Human alpha interferons (interferon alfa, IFN-alpha), interferon gamma (IFN-gamma) and monocytes have strong anti-neoplastic response in vitro and in vivo
- IFN-alpha and IFN-gamma have been shown in early phase clinical trials to be safely administered intraperitoneally.
- Intraperitoneal monocytes alone or activated with IFN-gamma are safe and feasible as demonstrated in phase I clinical studies.
- We have shown that the combination of human monocytes, IFN-alpha2a and IFN-gamma1b, or pegylated IFN-alpha, act synergistically against tumor cells in vitro and in mouse models.
Objectives:
-To identify a maximum tolerated dose of intraperitoneal autologous monocytes and Sylatron(R) (Peginterferon alfa-2b) and Actimmune(R) (Interferon gamma-1b).
Eligibility:
- Advanced metastatic or unresectable epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer that is relapsed and resistant or refractory to prior platinum-based standard care systemic regimen.
- Patients must be off prior chemotherapy, radiation therapy, hormonal therapy or biological therapy for at least 4 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 and adequate organ and marrow function.
Design:
- This is an open label single arm phase I trial to determine the maximum tolerated dose of intraperitoneal monocytes and Sylatron(R) (Peginterferon alfa-2b) and Actimmune(R) (Interferon gamma-1b).
- Autologous monocytes obtained through apheresis will be mixed with Sylatron(R) (Peginterferon alfa-2b) and Actimmune(R) (Interferon gamma-1b) in a 3 + 3 dose escalation and administered intraperitoneally once every 28 days. A new product will be manufactured for each treatment cycle.
- Once the maximum tolerated dose is obtained, an expansion cohort will be enrolled to better quantify response rate and time to disease progression.
- Research samples including peripheral blood and ascites will be obtained prior to the initiation of study therapy andprior to the start of each cycle. Tissue biopsies will be obtained in the dose expansion phase to characterize the immune infiltration.
- Patients will be evaluated every 2 cycles for response using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and every cycle for safety using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
- Being tested
- Autologous Monocytes + ACTIMMUNE + SYLATRON
- Keywords
- Immunotherapy, Adoptive Cell Therapy, Carcinomatosis, CA125
- Medical subject headings
- Fallopian Tube Neoplasms, Ovarian Neoplasms, Carcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous Monocytes + ACTIMMUNE + SYLATRONBiological
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).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: Autologous Monocytes + ACTIMMUNE + SYLATRON |
| EX1 Dose Expansion Arm | Experimental | 10 additional patients will be treated at the maximum tolerated dose (MTD) Receives: Biological: Autologous Monocytes + ACTIMMUNE + SYLATRON |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Maximum Tolerated Dose of Intraperitoneal Autologous Monocytes
Maximum Tolerated Dose of intraperitoneal autologous monocytes.
Measured: Cycle 1 Day 28
Overall Maximum Tolerated Dose of Sylatron (Peginterferon Alpha-2b)
Maximum Tolerated Dose of Sylatron (Peginterferon alpha-2b).
Measured: Cycle 1 Day 28
Overall Maximum Tolerated Dose of Actimmune (Interferon Gamma-1b)
Maximum Tolerated Dose of Actimmune (Interferon gamma-1b).
Measured: Cycle 1 Day 28
Secondary outcomes (2)
Number of Participants With a Response
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response (CR) is disappearance of all target lesions. Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD) is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.
Measured: Participants were evaluated for response by radiographic imaging every 8 weeks, up to 80 weeks
Time to Disease Progression
Time to disease progression is defined as the time from registration to progression, censored at date last known progression-free for those who have not progressed. Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study
Measured: Participants were assessed every 4 weeks by physical exam and 8 weeks by radiographic imaging for disease progression, up to 10 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2016 (estimated)
- Study start8 Feb 2017
- Primary completion29 Sep 2020
- Study completion29 Sep 2020
Why it stopped: Study was closed to accrual due to lack of drug supply.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Fallopian Tube CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Stanley Lipkowitz, MD, PhD, National Cancer Institute (NCI)
- Investigators
- Stanley Lipkowitz, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02948426
- Sponsor's protocol ID
- 170011
- Other IDs
- 17-C-0011
- Status last verified
- Dec 2025
- First submitted
- 27 Oct 2016
- Last updated
- 8 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).
Publications
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.
PubMed 25068849Soderquest 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.
PubMed 21389319Artis D, Spits H. The biology of innate lymphoid cells. Nature. 2015 Jan 15;517(7534):293-301. doi: 10.1038/nature14189.
PubMed 25592534Phase 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
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
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.
PubMed 30012146Green 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.
PubMed 30871636First-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
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.
PubMed 33278077
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of 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
- ClinicalTrials.gov ID
- NCT02948426
- Acronym / sponsor ID
- 170011
- Keywords
- Immunotherapy, Adoptive Cell Therapy, Carcinomatosis, CA125
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was closed to accrual due to lack of drug supply.
- Enrolment
- 18 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 8 Feb 2017 (actual)
- Primary completion
- 29 Sep 2020 (actual)
- Study completion
- 29 Sep 2020 (actual)
- First posted
- 28 Oct 2016 (estimated)
- Results
- Posted 16 Jun 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background:
- Monocytes can differentiate into classic M1 (classically activated) macrophages inhibiting tumor proliferation and promoting natural killer (NK) cell differentiation.
- Human alpha interferons (interferon alfa, IFN-alpha), interferon gamma (IFN-gamma) and monocytes have strong anti-neoplastic response in vitro and in vivo
- IFN-alpha and IFN-gamma have been shown in early phase clinical trials to be safely administered intraperitoneally.
- Intraperitoneal monocytes alone or activated with IFN-gamma are safe and feasible as demonstrated in phase I clinical studies.
- We have shown that the combination of human monocytes, IFN-alpha2a and IFN-gamma1b, or pegylated IFN-alpha, act synergistically against tumor cells in vitro and in mouse models.
Objectives:
-To identify a maximum tolerated dose of intraperitoneal autologous monocytes and Sylatron(R) (Peginterferon alfa-2b) and Actimmune(R) (Interferon gamma-1b).
Eligibility:
- Advanced metastatic or unresectable epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer that is relapsed and resistant or refractory to prior platinum-based standard care systemic regimen.
- Patients must be off prior chemotherapy, radiation therapy, hormonal therapy or biological therapy for at least 4 weeks.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1 and adequate organ and marrow function.
Design:
- This is an open label single arm phase I trial to determine the maximum tolerated dose of intraperitoneal monocytes and Sylatron(R) (Peginterferon alfa-2b) and Actimmune(R) (Interferon gamma-1b).
- Autologous monocytes obtained through apheresis will be mixed with Sylatron(R) (Peginterferon alfa-2b) and Actimmune(R) (Interferon gamma-1b) in a 3 + 3 dose escalation and administered intraperitoneally once every 28 days. A new product will be manufactured for each treatment cycle.
- Once the maximum tolerated dose is obtained, an expansion cohort will be enrolled to better quantify response rate and time to disease progression.
- Research samples including peripheral blood and ascites will be obtained prior to the initiation of study therapy andprior to the start of each cycle. Tissue biopsies will be obtained in the dose expansion phase to characterize the immune infiltration.
- Patients will be evaluated every 2 cycles for response using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and every cycle for safety using Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 - Sylatron 25µg (0.1 µg/ml); Actimmune 5mg (0.02µg/ml) | Experimental | Biological: Autologous Monocytes + ACTIMMUNE + SYLATRONSylatron 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. |
| Dose Level 2 - Monocytes (75x10^6); Sylatron 25µg (0.1µg/ml); Actimmune 5mg (0.02µg/ml) | Experimental | Biological: Autologous Monocytes + ACTIMMUNE + SYLATRONMonocytes (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. |
| Dose Level 3 - Monocytes (750x10^6); Sylatron 25µg (0.1µg/ml); Actimmune 5mg (0.02µg/ml) | Experimental | Biological: Autologous Monocytes + ACTIMMUNE + SYLATRONMonocytes (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. |
| Dose Level 4 - Monocytes (750x10^6); Sylatron 250µg (1µg/ml); Actimmune 50mg (0.2µg/ml) | Experimental | Biological: Autologous Monocytes + ACTIMMUNE + SYLATRONMonocytes (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. |
| EX1 Dose Expansion Arm | Experimental | Biological: Autologous Monocytes + ACTIMMUNE + SYLATRON10 additional patients will be treated at the maximum tolerated dose (MTD) |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (15 listed)
- Patients who are receiving any other investigational agents (with exception of imaging agents as indicated above in the inclusion criteria).
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous Monocytes + ACTIMMUNE + SYLATRONThe 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). | Biological | 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 |
Primary outcome
Overall Maximum Tolerated Dose of Intraperitoneal Autologous Monocytes
Time frame: Cycle 1 Day 28
Maximum Tolerated Dose of intraperitoneal autologous monocytes.
Overall Maximum Tolerated Dose of Sylatron (Peginterferon Alpha-2b)
Time frame: Cycle 1 Day 28
Maximum Tolerated Dose of Sylatron (Peginterferon alpha-2b).
Overall Maximum Tolerated Dose of Actimmune (Interferon Gamma-1b)
Time frame: Cycle 1 Day 28
Maximum Tolerated Dose of Actimmune (Interferon gamma-1b).
2 secondary outcomes
Number of Participants With a Response
Time frame: Participants were evaluated for response by radiographic imaging every 8 weeks, up to 80 weeks
Time to Disease Progression
Time frame: Participants were assessed every 4 weeks by physical exam and 8 weeks by radiographic imaging for disease progression, up to 10 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25068849Johnson 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.
- Background: PubMed 21389319Soderquest 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.
- Background: PubMed 25592534Artis D, Spits H. The biology of innate lymphoid cells. Nature. 2015 Jan 15;517(7534):293-301. doi: 10.1038/nature14189.
- BackgroundPhase 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
- BackgroundProduction 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: PubMed 30012146Green 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.
- Background: PubMed 30871636Green 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.
- Results publicationFirst-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
- Derived from this study: PubMed 33278077Kamat 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.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request. In addition, all large-scale genomic sequencing data will be shared with subscribers to the database of Genotypes and Phenotypes (dbGaP).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stanley Lipkowitz, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Autologous Monocytes + ACTIMMUNE + SYLATRON in people with Fallopian Tube Cancer and Ovarian Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Maximum Tolerated Dose of Intraperitoneal Autologous Monocytes (time frame: Cycle 1 Day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02948426, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2026.