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

NCT04902443 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 21002321-C-0023
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Viral Associated Malignancies; Kaposi Sarcoma; EBV/KSHV-associated Lymphomas

Keywords

AIDS; Small Molecule Inhibitor; Immune Therapy; PD-L1

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of pomalidomide with nivolumab

  The fraction of participants with toxicity noted at each dose level will be reported by grade and type of toxicity identified. Maximum tolerated dose will also be reported.

  24 months of treatment, until confirmed progression, unacceptable toxicity or trial withdrawal

Secondary Outcomes (1)

• anti-tumor activity and clinical benefits

  Every month (+/-1week) for 100 days after stopping treatment; then every 3 months (+/-2 weeks) for 1 year following end-of-treatment; then every 6 months

Study Arms (3)

1/Dose De-Escalation

EXPERIMENTAL

Treatment with pomalidomide at de-escalating doses if necessary and nivolumab at a fixed dose - CLOSED

Drug: Pomalidomide; Drug: Nivolumab

2/Dose Escalation

EXPERIMENTAL

Treatment with pomalidomide at escalating doses and nivolumab at a fixed dose

Drug: Pomalidomide; Drug: Nivolumab

3/Dose Expansion

EXPERIMENTAL

Nivolumab + pomalidomide (at optimal dose determined in dose escalation portion of the study) for up to 30 participants

Drug: Pomalidomide; Drug: Nivolumab

Interventions

Pomalidomide DRUG

Pomalidomide will be administered as an oral planned starting dose of 3 mg daily (dose escalation) or at an MTD of 4 mg (dose expansion). Pomalidomide will be given from day 1 to day 21 of each cycle.

1/Dose De-Escalation; 2/Dose Escalation; 3/Dose Expansion

Nivolumab DRUG

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

1/Dose De-Escalation; 2/Dose Escalation; 3/Dose Expansion

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically proven selected virus-associated tumors that are systemic, metastatic or locally advanced and not amenable to curative treatment options or are relapsed/refractory to first-line therapy as appropriate for each tumor type as outlined below. Also, participants with eligible solid tumors, who after evaluation by an expert in the area are deemed to be potentially curable after extensive surgery, but refuse such surgical procedure due to associated disfigurement and/or morbidity, may be eligible for the study with the necessary informed consent. Pathology confirmation by NCI Laboratory of Pathology is needed for eligibility.
• The following tumor types listed below are eligible, and require assessing of virus infection of the tumor cells with EBV EBER by in situ hybridization (ISH), KSHV LANA , p16, and Merkel cell polyomavirus large T antigen by immunohistochemistry (IHC) to document the respective viral infection (EBV, KSHV, HPV, MCPvY); or detection of serum HBV surface antigen, anti-HBV core antibody, elevated HBV DNA viral load, positive HVC antibody or elevated HCV RNA viral load. The tumor types studied in the phase 1 trial will be as below. For tumors where \>95% are known to be virus-associated, such as cervical cancer, confirmation of virus status is not required.
• EBV-positive Hodgkin lymphoma meeting the following criteria:
• Relapsed or refractory de novo classical Hodgkin lymphoma having failed standard first-line therapy; and
• Unresponsive or progressive disease after treatment with brentuximab vedotin or may be brentuximab vedotin na(SqrRoot) ve but is ineligible or unable to receive brentuximab vedotin; and
• Unresponsive or progressive disease after checkpoint inhibitor therapy;
• and
• Unresponsive or progressive disease after or is ineligible for autologous stem cell transplant (auto-SCT)
• EBV-positive aggressive non-Hodgkin lymphomas meeting the following criteria:
• Relapsed/refractory disease after standard first-line chemotherapy; and
• Relapsed disease after autologous stem cell transplant if indicated for histology (i.e diffuse large B-cell lymphoma relapsed more than one year after first line treatment) or autologous stem cell transplant is not feasible; and
• Relapsed after CAR-T cell therapy for HIV-negative participants only if indicated for histology (i.e diffuse large B-cell lymphoma) or CAR-T cell therapy is not feasible
• EBV-positive nasopharyngeal cancer unresponsive or progressive disease on or after platinum-containing chemotherapy and/or radiotherapy
• EBV-positive gastric cancer that is unresponsive or progressive disease on or after first-line chemotherapy
• EBV-positive leiomyosarcomas that is unresponsive or progressive disease on or after 2 systemic regimens (CCRT/platinum-taxane)

You may not qualify if:

• Participants who have had anticancer treatment within the last 2 weeks, unless the cancer treatment is for a malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial, such as local treatment for carcinoma in situ or hormonal therapy for prostate or breast carcinoma.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) with the following exceptions:
• Elevated triglyceride attributed to ART and/or HIV (must be \<= Grade 2)
• Alopecia, neuropathy and ototoxicity (i.e., AEs that are not expected to improve within the washout period)
• Participants who are receiving any other investigational agents.
• Participants will be excluded if they are on systemic steroid therapy that cannot be discontinued, with the exception of the use of prednisone or equivalent \<0.125mg/kg/day as replacement therapy. Inhaled or topical steroids are permitted.
• History of allergic reactions attributed to pomalidomide and/or nivolumab or compounds of similar chemical or biologic composition to pomalidomide and/or nivolumab.
• Participants who have received prior allogeneic stem cell or organ transplant.
• Participants with severe uncontrolled intercurrent illness.
• Cirrhosis with Child-Pugh score of B or C
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant and nursing persons are excluded from this study because pomalidomide is a thalidomide analog. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. These potential risks may also apply to nivolumab based on its mechanism of action and data from animal studies. In animal reproduction studies, administration of nivolumab to cynomolgus monkeys from the onset of organogenesis through delivery resulted in increased abortion and premature infant death.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Sarcoma, Kaposi; Acquired Immunodeficiency Syndrome

Interventions

pomalidomide; Nivolumab

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Ramya M Ramaswami, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Irene B Ekwede, R.N.

CONTACT

(240) 760-6126; irene.ekwede@nih.gov

Ramya M Ramaswami, M.D.

CONTACT

(240) 506-1088; ramya.ramaswami@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2021
• First Posted: May 26, 2021
• Study Start: December 10, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 28, 2026

Record last verified: 2026-04-24

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@@@@@@@Requests for all collected IPD data from clinical trials, conducted under a binding collaborative agreement between NCI/DCTD and a pharmaceutical/biotechnology company, that are not under DSMB monitoring must be in compliance with the terms of the binding collaborative agreement and must be approved by NCI/DCTD and the Pharmaceutical Collaborator (i.e., the NCI ETCTN Director in conjunction with the NCI/DCTD Regulatory Affairs Branch)

Locations

US (1)