Pomalidomide and Nivolumab in People With Virus-Associated Malignancies With or Without HIV

Kaposi Sarcoma Clinical Trial

Official title: A Phase I Study of Pomalidomide and Nivolumab in Patients With Virus-Associated Malignancies With or Without HIV

Status Recruiting

Clinical Trial Summary

Background:

Less toxic and more effective treatments are needed for cancers caused by viruses. These cancers include Hodgkin and non-Hodgkin lymphoma, hepatocellular carcinoma, head and neck cancer, nasopharyngeal carcinoma, gastric cancer, anal cancer, cervical cancer, vaginal cancer, vulvar cancer, penile cancer, Merkel cell carcinoma, Kaposi sarcoma, and leiomyosarcoma. Researchers want to see if a combination of drugs can help.

Objective:

To find a safe dose of pomalidomide plus nivolumab in people with cancers caused by viruses.

Eligibility:

Adults ages 18 or older who have cancers caused by Epstein Barr virus (EBV), human herpes virus 8/Kaposi sarcoma herpesvirus (HHV8/KSHV), human papilloma virus (HPV), hepatitis B or C virus (HBV/HCV), and Merkel cell polyomavirus (MCPyV) that have not responded to previous treatments or have relapsed, or in adults who do not want to have surgery because of disfigurement or other risks. Adults who have HIV with any CD4 T cell count are eligible.

Design:

Participants will be screened with blood and urine tests, scans, and heart tests. They will have a physical exam. Their ability to perform normal daily activities will be assessed. They may have a tumor biopsy.

Treatment will be given in 28-day cycles. Participants will take pomalidomide as a tablet by mouth for 21 days of each cycle, for up to 24 cycles. They will get nivolumab by intravenous infusion once each cycle. They will take an aspirin each day until 30 days after their last dose of the study drugs.

Participants will keep a pill diary. They will bring it to their study visit at the end of each cycle. At these visits, some screening tests will be repeated. Participants with Kaposi sarcoma will have pictures taken of their lesions.

Participants will give blood and saliva samples for research. They may have optional anal and/or cervical swabs. They may have optional biopsies.

Participants will have a follow-up visit 30 days after they stop taking the study drugs, then every month for 100 days. Some screening tests will be repeated. Then they may by contacted by phone every 3 months for 9 months, and then every 6 months thereafter....

Clinical Trial Description

Background:

• There is an unmet need for less toxic and more effective treatments for virus-associated malignancies.

• Pomalidomide induces polyfunctional T cell, NK cell, and dendritic cell activation.

• Pomalidomide has shown promising activity in Kaposi sarcoma, likely due in part to immune modulation.

• Downregulation and/or deregulation of immune surface markers by viruses can thwart immunologic therapy, which may be prevented or reversed by pomalidomide.

• PD-L1 is expressed in virus-associated malignancies and modulation of PD-1 signaling is a promising approach to treatment of virus-associated malignancies.

• Checkpoint inhibitors used alone have been shown to have some activity in certain virus-induced tumors (e.g. Hodgkin and non-Hodgkin lymphomas, Merkel cell carcinoma, and HPV-associated nasopharyngeal cancer). It is thus rational to explore combination strategies that overcome viral-mediated immune evasion and provide potentially better immunologic anti-tumor activity.

Objectives:

-Assess the safety and tolerability of pomalidomide plus nivolumab (Pom/Nivo) in participants with virus-associated solid malignancies

Eligibility:

• Age greater than or equal to 18 years

• Histologically or cytologically proven selected virus-associated tumors that are systemic, metastatic or locally advanced and not amenable to curative treatment options or relapsed/refractory to first-line therapy

• For solid tumors or hematologic malignancies at least one measurable disease

• At least five measurable cutaneous KS lesions with no previous local radiation, surgical or intralesional cytotoxic therapy to these measurable lesions.

• ECOG Performance Status (PS) less than or equal to 2

• Participants must be willing to give informed consent.

• Participants can be HIV positive or negative.

• Antiretroviral therapy (ART) for HIV+ patients

• Participants receiving other investigational agents will not be eligible.

Design:

• This is a Phase I study assessing the safety and efficacy of a fixed dose of nivolumab combined with increasing doses of pomalidomide in participants with viral associated malignancies.

• Up to 6 participants treated in a 3+3 dose de-escalation schema for pomalidomide using one dose de-escalation and one dose escalation levels.

• Following identification of an optimal dose, an expansion phase will be initiated through a protocol amendment. Up to 30 participants will be enrolled. Of these 12 participants must have a KS diagnosis and 12 participants must have EBV and/or KSHV-associated lymphomas.

• Nivolumab will be administered IV at a dose of 480 mg at day one of each cycle, except for cycle one when it will be administered on day 8. One cycle equals 28 days.

• Pomalidomide will be administered as an oral planned starting dose of 3 mg daily. Pomalidomide will be given from day 1 to day 21 of each cycle.

• Participants will receive therapy up to 24 cycles or until unacceptable toxicity, clinical progression, the participant s request to discontinue therapy, or PI decision. ;

Related Conditions & MeSH terms

• Kaposi Sarcoma
• Neoplasms
• Sarcoma, Kaposi

• NCT number: NCT04902443
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Irene Ekwede, R.N.
• Phone: (240) 760-6126
• Email: irene.ekwede@nih.gov
• Status: Recruiting
• Phase: Phase 1
• Start date: December 10, 2021
• Completion date: December 1, 2026