Last updated on June 2018

Nivolumab and Ipilimumab in Treating Patients With HIV Associated Relapsed or Refractory Classical Hodgkin Lymphoma or Solid Tumors That Are Metastatic or Cannot Be Removed by Surgery


Brief description of study

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 or does not respond to treatment, or solid tumors that have spread to other places in the body or cannot be removed by surgery. Monoclonal antibodies, such as ipilimumab and nivolumab, may block tumor growth in different ways by targeting certain cells. Ipilimumab is an antibody that acts against a molecule called cytotoxic T-lymphocyte antigen 4 (CTLA-4). CTLA-4 controls a part of your 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.

Detailed Study Description

PRIMARY OBJECTIVES:

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 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). Only single agent nivolumab will be utilized in the cHL cohort. (Solid Tumor Dose Expansion and cHL Cohorts)

TERTIARY 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.

II. 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.

III. 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.

IV. To understand the response of human tumor viruses (human papillomavirus [HPV], Epstein-Barr virus [EBV], Kaposi's sarcoma-associated herpesvirus [KSHV]) to agent.

V. To evaluate the effects of single agent nivolumab, and the combination of ipilimumab and nivolumab on herpesvirus loads (EBV, KSHV, cytomegalovirus [CMV]) in plasma.

VI. 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).

VII. 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.

VIII. 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.

IX. 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.

X. Understand the response of HIV to agent. XI. To evaluate the effects of single agent nivolumab, and the combination of ipilimumab and nivolumab on latent HIV loads in PBMC using outgrowth assay.

XII. 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 60 minutes on day 1. Patients in dose level 2 also receive ipilimumab IV over 90 minutes on day 1 of every third course of nivolumab, and patients in dose level -2 also receive ipilimumab IV over 90 minutes on day 1 of every sixth course of nivolumab. Courses repeat every 14 days for up to 46 courses of nivolumab (with ipilimumab if receiving dose level 2 or -2) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 16 weeks or 112 days (based on 5 half lives).

Clinical Study Identifier: NCT02408861

Contact Investigators or Research Sites near you

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Ronald T. Mitsuyasu

UCLA Center for Clinical AIDS Research and Education
Los Angeles, CA United States
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Scott D. Christensen

University of California Davis Comprehensive Cancer Center
Sacramento, CA United States
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William Wachsman

University of California San Diego
San Diego, CA United States
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Chia-Ching (Jackie) Wang

Zuckerberg San Francisco General Hospital
San Francisco, CA United States
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Chia-Ching (Jackie) Wang

UCSF Medical Center-Mount Zion
San Francisco, CA United States
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Juan C. Ramos

University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, FL United States
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Paul G. Rubinstein

John H Stroger Jr Hospital of Cook County
Chicago, IL United States
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Nina D. Wagner-Johnston

Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, MD United States
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Lee Ratner

Siteman Cancer Center at Washington University
Saint Louis, MO United States
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Lee Ratner

Washington University School of Medicine
Saint Louis, MO United States
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Lakshmi Rajdev

Montefiore Medical Center-Einstein Campus
Bronx, NY United States
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Lakshmi Rajdev

Montefiore Medical Center-Weiler Hospital
Bronx, NY United States
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Lakshmi Rajdev

Montefiore Medical Center - Moses Campus
Bronx, NY United States
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Michael S. Lee

UNC Lineberger Comprehensive Cancer Center
Chapel Hill, NC United States
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Robert A. Baiocchi

Ohio State University Comprehensive Cancer Center
Columbus, OH United States
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Douglas F. Beach

University of Pennsylvania/Abramson Cancer Center
Philadelphia, PA United States
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Douglas F. Beach

Pennsylvania Oncology Hematology Associates
Philadelphia, PA United States
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David M. Aboulafia

Benaroya Research Institute at Virginia Mason
Seattle, WA United States
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Lakshmi Rajdev

Virginia Mason Medical Center
Seattle, WA United States
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Manoj P. Menon

Harborview Medical Center
Seattle, WA United States
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Manoj P. Menon

Seattle Cancer Care Alliance
Seattle, WA United States
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Mark N. Polizzotto

Saint Vincent's Hospital
Darlinghurst, Australia
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Mark A. Dickson

Memorial Sloan Kettering Cancer Center
New York, NY United States
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Lakshmi Rajdev

UC San Diego Moores Cancer Center
La Jolla, CA United States
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Chia-Ching (Jackie) Wang

UCSF Medical Center-Parnassus
San Francisco, CA United States
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Lee Ratner

Barnes-Jewish Hospital
Saint Louis, MO United States
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Mark A. Dickson

Memorial Sloan Kettering Monmouth
Middletown, NJ United States
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Mark A. Dickson

Memorial Sloan Kettering Commack
Commack, NY United States
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Mark A. Dickson

Memorial Sloan Kettering Westchester
Harrison, NY United States
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Mark A. Dickson

Memorial Sloan Kettering Rockville Centre
Rockville Centre, NY United States
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Recruitment Status: Open


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