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

Stopped early · Phase 1

Conditions studied: Advanced Malignant Solid Neoplasm, Anal Carcinoma, HIV Infection, Kaposi Sarcoma, Lung Carcinoma, Metastatic Malignant Solid Neoplasm, Recurrent Classic Hodgkin Lymphoma, Refractory Classic Hodgkin Lymphoma, Unresectable Solid Neoplasm, HIV-associated Cancers

In brief

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.

Key facts

Study ID

NCT02408861

Run by

National Cancer Institute (NCI)

People needed

79

Starts

2015-10-21

Expected to finish

2024-08-31

Last updated by the study team

2026-01-21

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Participants must have histologically confirmed solid tumor malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective; participants with uncontrolled Kaposi sarcoma are permitted (KS must be increasing despite HAART and HIV suppression for greater than or equal to 2 months, or stable KS despite HAART for greater than or equal to 3 months)
• For participants in the 24 participant solid tumor cohort, only those histologies not known to respond to single agent nivolumab (such as pancreas, prostate, and microsatellite stable [MSS] colorectal cancer) will be excluded
• For participants in the relapsed refractory HIV-cHL expansion cohort, participants must have histologically confirmed, relapsed/refractory (defined as relapsed/refractory to one or greater lines of therapy) HIV-associated classical Hodgkin lymphoma
• HIV-1 infection, as documented by any federally approved, licensed HIV rapid test performed in conjunction with screening (or enzyme linked immunosorbent assay [ELISA], test kit, and confirmed by Western blot or other approved test); alternatively, this documentation may include a record demonstrating that another physician has documented the participant's HIV status based on either: 1) approved diagnostic tests, or 2) the referring physician's written record that HIV infection was documented, with supporting information on the participant's relevant medical history and/or current management of HIV infection
• Participants must have measurable disease, 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 >= 20 mm with conventional techniques or as >= 10 mm with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or calipers by clinical exam; scans must have been performed within 4 weeks prior to registration; Note: for participants with Kaposi sarcoma, the following apply: at least five measurable cutaneous KS lesions or any number of lesions with systemic unresectable disease with no previous local radiation, surgical, or intralesional cytotoxic therapy that would prevent response assessment
• Prior therapy for metastatic disease permitted; at least 4 weeks must have elapsed since prior chemotherapy or biological therapy, 6 weeks if the regimen included carmustine (BCNU) or mitomycin C; radiotherapy must be completed at least 4 weeks prior to registration
• Age > 18 years, because no dosing or AE data are currently available on the use of ipilimumab in combination with nivolumab in participants <18 years of age, children are excluded from this study.
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
• PARTICIPANTS NOT ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Leukocytes >= 2,000/mm\^3 (within 2 weeks prior to enrollment)
• PARTICIPANTS NOT ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Absolute neutrophil count >= 1,000/mm\^3 (within 2 weeks prior to enrollment)
• PARTICIPANTS NOT ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Platelets >= 75,000/mm\^3 (within 2 weeks prior to enrollment)
• PARTICIPANTS NOT ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) =< 3 x ULN for subjects with Gilbert's disease or with atazanavir- or indinavir-induced unconjugated hyperbilirubinemia without aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation and must have a total bilirubin less than 3.0 mg/dL (within 2 weeks prior to enrollment)
• PARTICIPANTS NOT ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Serum lipase and amylase < 1.5 x ULN (within 2 weeks prior to enrollment)
• PARTICIPANTS NOT ON THE HODGKIN LYMPHOMA EXPANSION COHORT: AST (serum glutamic oxaloacetic transaminase [SGOT])/ALT (serum glutamate pyruvate transaminase [SGPT]) =< 3 x ULN (within 2 weeks prior to enrollment)
• PARTICIPANTS NOT ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Creatinine < 1.5 UNL or creatinine clearance (CrCl) > 50 ml/min (within 2 weeks prior to enrollment)
• PARTICIPANTS NOT ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Hemoglobin >= 9 g/dL (within 2 weeks prior to enrollment)
• PARTICIPANTS NOT ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Serum albumin >= 2.8 g/dL (within 2 weeks prior to enrollment)
• PARTICIPANTS ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Leukocyte count: no lower limit (within 2 weeks prior to enrollment) (participants may receive granulocyte colony stimulating factor [GCSF] and transfusions to meet these parameters)
• PARTICIPANTS ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Absolute neutrophil count: >= 1,000/mm\^3, unless decreased due to bone marrow involvement with lymphoma (within 2 weeks prior to enrollment) (participants may receive GCSF and transfusions to meet these parameters)
• PARTICIPANTS ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Platelets: >= 75,000/mm\^3, unless decreased due to bone marrow involvement with lymphoma (within 2 weeks prior to enrollment) (participants may receive GCSF and transfusions to meet these parameters)
• PARTICIPANTS ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Hemoglobin: >= 9 g/dL unless bone marrow involvement secondary to Hodgkin lymphoma is present (within 2 weeks prior to enrollment) (participants may receive GCSF and transfusions to meet these parameters)
• PARTICIPANTS ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Total bilirubin: =< 1.5 x institutional upper limit of normal (ULN), or =< 3 x ULN for participants with Gilbert's disease or with atazanavir- or indinavir-induced unconjugated hyperbilirubinemia without AST or ALT elevation, and must have a total bilirubin less than 3.0 mg/dL) (within 2 weeks prior to enrollment) (participants may receive GCSF and transfusions to meet these parameters)
• PARTICIPANTS ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Serum lipase and amylase < 1.5 x ULN (within 2 weeks prior to enrollment) (participants may receive GCSF and transfusions to meet these parameters)
• PARTICIPANTS ON THE HODGKIN LYMPHOMA EXPANSION COHORT: AST (SGOT)/ALT (SGPT): =< 3 x ULN (within 2 weeks prior to enrollment) (participants may receive GCSF and transfusions to meet these parameters)
• PARTICIPANTS ON THE HODGKIN LYMPHOMA EXPANSION COHORT: Creatinine: < 1.5 x upper normal limit (UNL) or CrCl > 50ml/min (within 2 weeks prior to enrollment) (participants may receive GCSF and transfusions to meet these parameters)

You may not qualify if…

• Participants who have received any other investigational agents within the 4 weeks prior to enrollment; concurrent radiation therapy is not permitted, except palliative (limited-field) radiation therapy, if all of the following criteria are met:
• Repeat imaging demonstrates no new sites of bone metastases
• The lesion being considered for palliative radiation is not a target lesion
• Participants with known brain metastases or leptomeningeal metastases must be excluded unless they qualify for enrollment as described below because of poor prognosis and concerns regarding progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; participants with brain metastases are permitted if metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks or more after treatment is complete and within 4 weeks prior to the first dose of nivolumab administration
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ipilimumab, nivolumab, or other agents used in study, or history of severe hypersensitivity reaction to any monoclonal antibody
• Participants should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 2 weeks of study drug administration; these drugs may interfere with the activity of ipilimumab and nivolumab if administered at the time of the first ipilimumab dose; inhaled or topical steroids and adrenal replacement doses =< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; participants are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if >= 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted; use of anabolic steroids is permitted
• Participants with clinical or radiographic evidence of pancreatitis are excluded
• 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 that would limit compliance with study requirements
• Participants should be excluded if they have had prior treatment with an anti-PD-1, anti-programmed cell death ligand 1 (PD-L1), anti-programmed cell death ligand 2 (PD-L2), anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways; prior immune modulating therapy including vaccines may be eligible; prior immune events must be evaluated and the risk for new events which may represent continued sub clinical disease or a new process at previously damaged site or immune potentiation (e.g. ipilimumab followed by IL2 causing bowel perforation, ipilimumab followed by indoleamine 2,3-dioxygenase [IDO] inhibitor resulting in clinical hypophysitis); please keep in mind that inflammatory events may occur weeks to months following the last dose of ipilimumab and possibly nivolumab; assessment of potential effects of prior therapy should include:
• Immune status
• Organ damage
• Risk of autoimmunity
• Immunopotentiation
• The participant has not recovered to baseline or Common Terminology Criteria for Adverse Events (CTCAE) =< grade 1 from toxicity due to all prior therapies except =< grade 2 alopecia, neuropathy, and other non-clinically significant adverse events (AEs)
• The participant has a primary brain tumor
• Participant has >= grade 2 diarrhea (participants with grade 1 diarrhea are eligible provided stool for ova/parasites and stool cryptosporidium studies are negative)
• Opportunistic infection within the last 3 months
• Participants with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and participants with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease; participants with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible; participants with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and participants with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible; participants are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
• Participants who have had evidence of Clostridium (C.) difficile infection, active or acute diverticulitis, intra-abdominal abscess, intra-abdominal abscess, gastrointestinal (GI) obstruction and abdominal carcinomatosis, which are known risk factors for bowel perforation, should be evaluated for the potential need for additional treatment before coming on study
• cHL COHORT ONLY: history of allogeneic transplant

Where it is running

• UC San Diego Moores Cancer Center — La Jolla, California, United States
• UCLA Center for Clinical AIDS Research and Education — Los Angeles, California, United States
• University of California Davis Comprehensive Cancer Center — Sacramento, California, United States
• UC San Diego Medical Center - Hillcrest — San Diego, California, United States
• Zuckerberg San Francisco General Hospital — San Francisco, California, United States
• UCSF Medical Center-Mount Zion — San Francisco, California, United States
• UCSF Medical Center-Parnassus — San Francisco, California, United States
• George Washington University Medical Center — Washington D.C., District of Columbia, United States
• University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States
• Moffitt Cancer Center — Tampa, Florida, United States
• John H Stroger Jr Hospital of Cook County — Chicago, Illinois, United States
• Johns Hopkins University/Sidney Kimmel Cancer Center — Baltimore, Maryland, United States
• Siteman Cancer Center at Washington University — St Louis, Missouri, United States
• Washington University School of Medicine — St Louis, Missouri, United States
• Memorial Sloan Kettering Monmouth — Middletown, New Jersey, United States
• Memorial Sloan Kettering Commack — Commack, New York, United States
• Memorial Sloan Kettering Westchester — East White Plains, New York, United States
• Memorial Sloan Kettering Cancer Center — New York, New York, United States
• Montefiore Medical Center-Einstein Campus — The Bronx, New York, United States
• Montefiore Medical Center-Weiler Hospital — The Bronx, New York, United States
• Montefiore Medical Center - Moses Campus — The Bronx, New York, United States
• Memorial Sloan Kettering Nassau — Uniondale, New York, United States
• UNC Lineberger Comprehensive Cancer Center — Chapel Hill, North Carolina, United States
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States
• University of Pennsylvania/Abramson Cancer Center — Philadelphia, Pennsylvania, United States

Full record on ClinicalTrials.gov

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