Clinical Trials Logo

Clinical Trial Summary

This phase I trial studies the side effects and best dose of nivolumab when given with ipilimumab in treating patients with human immunodeficiency virus (HIV) associated classical Hodgkin lymphoma that has returned after a period of improvement (relapsed) or does not respond to treatment (refractory), or solid tumors that have spread from where it first started to other places in the body (metastatic) or cannot be removed by surgery (unresectable). Immunotherapy with monoclonal antibodies, such as ipilimumab and nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Ipilimumab is an antibody that acts against a molecule called cytotoxic T-lymphocyte antigen 4 (CTLA-4). CTLA-4 controls a part of the immune system by shutting it down. Nivolumab is a type of antibody that is specific for human programmed cell death 1 (PD-1), a protein that is responsible for destruction of immune cells. Giving ipilimumab with nivolumab may work better in treating patients with HIV associated classical Hodgkin lymphoma or solid tumors compared to ipilimumab with nivolumab alone.


Clinical Trial Description

PRIMARY OBJECTIVE: I. To demonstrate safety and feasibility of ipilimumab and nivolumab at the standard doses of drug in solid tumor and relapsed refractory HIV-classical Hodgkin lymphoma (cHL) participants with human immunodeficiency virus (HIV) infection given the possibility of increased toxicity based on immune activation, co-morbidity, or interference with highly active antiretroviral therapy (HAART) therapy. (Dose De-escalation and Dose Expansion Cohorts) SECONDARY OBJECTIVES: I. To evaluate the effects of single agent nivolumab, and the combination of ipilimumab and nivolumab, on immune function (HIV viral load in plasma using conventional assay, CD4+ and CD8+ cells). (Dose De-escalation Cohort) II. To preliminarily assess objective response rates associated with treatment for commonly represented solid tumors (Kaposi sarcoma, anal cancer, and lung cancer) and relapsed refractory HIV-cHL. (Solid Tumor Dose Expansion and cHL Cohorts) III. To evaluate the effects of single agent nivolumab, and the combination of ipilimumab and nivolumab, on immune function (HIV viral load in plasma using conventional HIV assay, CD4+, and CD8+ cells). (Solid Tumor Dose Expansion and cHL Cohorts) EXPLORATORY OBJECTIVES: I. Understand the immune response to agent in the context of antiretroviral therapy (ART), of altered immune function, and repertoire due to prior HIV infection. Ia. To evaluate the effects of single agent nivolumab, and the combination of ipilimumab and nivolumab, on intratumor immune cells by immunohistochemistry (IHC) such as PD1, programmed cell death 1 ligand 1 (PDL-1), and others. Ib. To evaluate the effects of single agent nivolumab, and the combination of ipilimumab and nivolumab on circulating cytokine markers by multiplex assay, such as: interleukin (IL)-2, IL-4, IL-6, IL-10, IL-8, interferon gamma-induced protein 10 (IP10), chemokine (C-X-C motif) ligand 13 (CXCL13), interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, soluble IL-2 receptor (sIL2R)-alpha, sCD27, soluble TNF receptor (sTNFR)1, and sTNFR2. II. To understand the response of human tumor viruses (human papillomavirus [HPV], Epstein-Barr virus [EBV], Kaposi's sarcoma-associated herpesvirus [KSHV]) to agent. IIa. To evaluate the effects of single agent nivolumab, and the combination of ipilimumab and nivolumab on herpesvirus loads (EBV, KSHV, cytomegalovirus [CMV]) in plasma. IIb. To evaluate the effects of single agent nivolumab, and the combination of ipilimumab and nivolumab on latent herpesvirus (EBV, KSHV, CMV) in peripheral blood mononuclear cells (PBMC). IIc. To evaluate the effects of single agent nivolumab, and the combination of ipilimumab and nivolumab on herpesvirus specific CD8 and CD4 T cells in PBMC. IId. In cases of Kaposi sarcoma, to evaluate the effects of single agent nivolumab, and the combination of ipilimumab and nivolumab on viral transcription in tumor biopsies. IIe. In cases of anal cancer, to evaluate the effects of single agent nivolumab, and the combination of ipilimumab and nivolumab on HPV types in anal swabs, when feasible. III. Understand the response of HIV to agent. IIIa. To evaluate the effects of single agent nivolumab, and the combination of ipilimumab and nivolumab on latent HIV loads in PBMC using outgrowth assay. IIIb. To evaluate the effects of single agent nivolumab, and the combination of ipilimumab and nivolumab on HIV reactive T cells. OUTLINE: This is a dose-escalation study of nivolumab. Patients receive nivolumab intravenously (IV) over 30 minutes on day 1. Patients in dose level 2 also receive ipilimumab IV over 90 minutes on day 1 of every third cycle of nivolumab, and patients in dose level -2 also receive ipilimumab IV over 90 minutes on day 1 of every sixth cycle of nivolumab. Treatment repeats every 14 days for up to 46 cycles of nivolumab (with ipilimumab if receiving dose level 2 or -2) in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study. Patients undergo positron emission tomography (PET) and computed tomography (CT) during screening and on study. Patients undergo bone marrow biopsy on screening and may undergo it during follow up. After completion of study treatment, patients are followed up for 16 weeks or 112 days (based on 5 half lives). ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02408861
Study type Interventional
Source National Cancer Institute (NCI)
Contact
Status Recruiting
Phase Phase 1
Start date October 21, 2015
Completion date July 1, 2024

See also
  Status Clinical Trial Phase
Active, not recruiting NCT02135419 - Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Lesions Phase 3
Active, not recruiting NCT02663856 - My Smart Age With HIV: Smartphone Self-assessment of Frailty
Completed NCT02846402 - Impact of HIV Self-testing Among Female Sex Workers in Kampala, Uganda N/A
Completed NCT02659306 - Metformin Immunotherapy in HIV Infection Phase 1
Completed NCT02663869 - Aging With HIV at Younger vs Older Age: a Diverse Population With Distinct Comorbidity Profiles
Terminated NCT02743598 - Liraglutide for HIV-associated Neurocognitive Disorder Phase 4
Completed NCT02921516 - Growing Up: Intervening With HIV-Positive Adolescents in Resource-Poor Settings N/A
Completed NCT02564341 - Targeting Effective Analgesia in Clinics for HIV - Intervention N/A
Active, not recruiting NCT02302950 - A Retrospective Analysis of Raltegravir Use in Minority HIV Infected Women in Houston, Texas N/A
Terminated NCT02109224 - Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection Phase 1
Completed NCT01852942 - Reversing Tissue Fibrosis to Improve Immune Reconstitution in HIV Phase 2
Completed NCT02269605 - Bryostatin-1 Effect on HIV-1 Latency and Reservoir in HIV-1 Infected Patients Receiving Antiretroviral Treatment Phase 1
Completed NCT01830595 - Lactoferrin Treatment in HIV Patients Phase 2
Terminated NCT01902186 - Bone Mineral Density Changes in HIV-positive Females With Osteopenia Switching to Raltegravir Phase 4
Completed NCT02525146 - Birmingham Access to Care Study N/A
Completed NCT02527135 - Text Messaging to Improve HIV Testing Among Young Women in Kenya N/A
Completed NCT01946217 - Factors Affecting Patient Participation in AIDS Malignancy Clinical Trials Consortium Clinical Trials N/A
Completed NCT02118168 - Observational Study for the Extended Follow-up of the Patients Enrolled in the Therapeutic Clinical Trial ISS T-002 N/A
Active, not recruiting NCT02602418 - Neural Correlates of Working Memory Training for HIV Patients N/A
Completed NCT01680094 - Safety and Effect of The HDAC Inhibitor Panobinostat on HIV-1 Expression in Patients on Suppressive HAART Phase 1/Phase 2