Study Stopped
Inadequate accrual rate
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
A Phase I Study of Ipilimumab and Nivolumab in Advanced HIV Associated Solid Tumors With Expansion Cohort in HIV Associated Solid Tumors and a Cohort of HIV-Associated Classical Hodgkin Lymphoma
5 other identifiers
interventional
79
2 countries
34
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2015
Longer than P75 for phase_1
34 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 3, 2015
CompletedFirst Posted
Study publicly available on registry
April 6, 2015
CompletedStudy Start
First participant enrolled
October 21, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 1, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
August 31, 2024
CompletedResults Posted
Study results publicly available
September 23, 2025
CompletedJanuary 21, 2026
September 1, 2025
8.5 years
April 3, 2015
July 16, 2025
January 5, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Maximum Tolerated Dose of Nivolumab
Will be defined as the starting dose level at which 1/6 subjects experience dose limiting toxicity (DLT) with the next higher dose having at least \>= 2 participants encountering DLT. Toxicity data will be presented by type and severity for each dose group and overall; the incidence of toxicity related dose reductions and treatment discontinuations will be summarized.
Each patient will be evaluated for DLT for the safety evaluation period of 6 weeks
Dose Limiting Toxicities (DLTs) Observed in Dose De-escalation Cohorts
Incidence of DLTs during the safety evaluation period of 6 weeks at a given dose from the first dose of treatment.
6 weeks from the first dose of Nivolumab
Incidence of Adverse Events According to NCI CTCAE v5.0
Number of adverse events that are either possibly, probably or definitely attributed to study intervention. In case an adverse event as per the CTCAE v5.0 occurs within a same patient, an instance with the highest severity of the adverse event is counted. Separate event-instances are reported otherwise.
Participants will be followed for 16 weeks or 112 days after removal from study treatment, or until death, whichever occurs first.
Secondary Outcomes (5)
Objective Response Rate
Up to 3 years
Immune Function, Defined as CD4 and CD8 Cell Counts at Baseline and at End of 46 Cycles of Treatment+ 6 Weeks
end of 46 cycles of treatment+ 6 weeks
Immune Function, Defined as CD4 and CD8 Cell Counts at Baseline and at End of 46 Cycles of Treatment+ 16 Weeks
end of 46 cycles of treatment+ 16 weeks
HIV Viral Load at Baseline and at End of 46 Cycles of Treatment+ 6 Weeks
end of 46 cycles of treatment+ 6 weeks
HIV Viral Load at Baseline and at End of 46 Cycles of Treatment+ 16 Weeks
end of 46 cycles of treatment+16 weeks
Other Outcomes (9)
Intratumor Immune Cells
Up to 3 years
Circulating Cytokine Markers
Up to 3 years
Herpesvirus Loads (Epstein-Barr Virus [EBV], Kaposi Sarcoma Herpes Virus [KSHV], Cytomegalovirus [CMV]) in Plasma
Up to 3 years
- +6 more other outcomes
Study Arms (7)
Dose De-escalation Single Agent Nivolumab Stratum 1
EXPERIMENTALStratum 1 will enroll participants with T lymphocyte CD4+ count above 200/mm3. Stratum 1 dosing will start with a full dose of nivolumab 3 mg/kg (dose level 1) and one dose de-escalation is allowed; after evaluating dosing for single agent nivolumab. No intra-participant dose escalations will be allowed. The safety evaluation period is 6 weeks at a given dose level.
Dose De-escalation Single Agent Nivolumab Stratum 2
EXPERIMENTALStratum 2 will enroll participants with T lymphocyte CD4+ count between 100 to 200/mm3. Stratum 2 will start enrolling after completion of stratum 2 dose deescalation. The dosing will begin at the single-agent therapy MTD for Stratum 1 (dose level 1 or -1). Stratum 2 will not be allowed to escalate beyond the MTD for Stratum 1. Only 1 dose de-escalation will be allowed.
Dose De-escalation Cohort Combination Therapy (Nivolumab and Ipilimumab) Stratum 1
EXPERIMENTALStratum 1 dosing will start with a full dose of nivolumab 3 mg/kg (dose level 1) and one dose de-escalation is allowed; Participants will be treated with 240 mg of nivolumab and 1 mg/kg of ipilimumab will be added to evaluate combination therapy (dose level 2) with one dose de- escalation allowed. No intra-participant dose escalations will be allowed. The safety evaluation period is 6 weeks at a given dose level.
Dose De-escalation Cohort Combination Therapy (Nivolumab and Ipilimumab) Stratum 2
EXPERIMENTALStratum 2 will enroll participants with lymphocyte T CD4+ count between 100-200/mm3 Participants will be treated with 240 mg of nivolumab and 1 mg/kg of ipilimumab will be added to evaluate combination therapy (dose level 2) with one dose de- escalation allowed. No intra-participant dose escalations will be allowed. The safety evaluation period is 6 weeks at a given dose level.
Solid Tumors Dose Expansion Cohort Single Agent Nivolumab
EXPERIMENTALParticipants with incurable solid tumors will be treated at single agent nivolumab 240 mg every 2 weeks. Only those histologies that are not known to respond to single agent nivolumab will be excluded (i.e., pancreas, prostate, MSS colorectal cancer, unless results from another clinical trial showing non-response in another tumor type become available in the future). Up to 24 participants will be enrolled.
Combination Regimen Expansion Cohort
EXPERIMENTALThe combination therapy at MTD of Nivolumab and Ipilimumab regimen will be studied in a dose expansion cohort (up to 12 participants) limited to only participants with Kaposi sarcoma, lung cancer, and anal cancer.
Classical Hodgkin Lymphoma Cohort
EXPERIMENTALSingle agent Nivolumab therapy at MTD dose from dose-de-escalation will be administered in participants with classical Hodgkin's Lymphoma with a fixed dose of 240 mg q 2 week.
Interventions
Undergo blood sample collection
Undergo bone marrow biopsy
Undergo CT scan
Given IV
Given IV
Undergo PET scan
Eligibility Criteria
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)
- +23 more criteria
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
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (34)
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
UCLA Center for Clinical AIDS Research and Education
Los Angeles, California, 90035, United States
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817, United States
UC San Diego Medical Center - Hillcrest
San Diego, California, 92103, United States
Zuckerberg San Francisco General Hospital
San Francisco, California, 94110, United States
UCSF Medical Center-Mount Zion
San Francisco, California, 94115, United States
UCSF Medical Center-Parnassus
San Francisco, California, 94143, United States
George Washington University Medical Center
Washington D.C., District of Columbia, 20037, United States
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
John H Stroger Jr Hospital of Cook County
Chicago, Illinois, 60612, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Siteman Cancer Center at Washington University
St Louis, Missouri, 63110, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Memorial Sloan Kettering Monmouth
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
East White Plains, New York, 10604, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
Montefiore Medical Center-Weiler Hospital
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104, United States
Pennsylvania Hospital
Philadelphia, Pennsylvania, 19107, United States
Temple University Hospital
Philadelphia, Pennsylvania, 19140, United States
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
Benaroya Research Institute at Virginia Mason
Seattle, Washington, 98101-2795, United States
Virginia Mason Medical Center
Seattle, Washington, 98101, United States
Harborview Medical Center
Seattle, Washington, 98104, United States
FHCC South Lake Union
Seattle, Washington, 98109, United States
Saint Vincent's Hospital
Darlinghurst, New South Wales, 2010, Australia
University of New South Wales
Sydney, New South Wales, 2052, Australia
Related Publications (2)
Rajdev L, Jackie Wang CC, Joshi H, Lensing S, Lee J, Ramos JC, Baiocchi R, Ratner L, Rubinstein PG, Ambinder R, Henry D, Streicher H, Little RF, Chiao E, Dittmer DP, Einstein MH, Cesarman E, Mitsuyasu R, Sparano JA; AIDS Malignancy Consortium. Assessment of the safety of nivolumab in people living with HIV with advanced cancer on antiretroviral therapy: the AIDS Malignancy Consortium 095 Study. Cancer. 2024 Mar 15;130(6):985-994. doi: 10.1002/cncr.35110. Epub 2023 Nov 14.
PMID: 37962072DERIVEDRasmussen TA, Rajdev L, Rhodes A, Dantanarayana A, Tennakoon S, Chea S, Spelman T, Lensing S, Rutishauser R, Bakkour S, Busch M, Siliciano JD, Siliciano RF, Einstein MH, Dittmer DP, Chiao E, Deeks SG, Durand C, Lewin SR. Impact of Anti-PD-1 and Anti-CTLA-4 on the Human Immunodeficiency Virus (HIV) Reservoir in People Living With HIV With Cancer on Antiretroviral Therapy: The AIDS Malignancy Consortium 095 Study. Clin Infect Dis. 2021 Oct 5;73(7):e1973-e1981. doi: 10.1093/cid/ciaa1530.
PMID: 33677480DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr Himanshu Joshi MBBS MPH PhD
- Organization
- Icahn School of Medicine at Mount Sinai
Study Officials
- PRINCIPAL INVESTIGATOR
Lakshmi Rajdev
AIDS Malignancy Consortium
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
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
April 3, 2015
First Posted
April 6, 2015
Study Start
October 21, 2015
Primary Completion
May 1, 2024
Study Completion
August 31, 2024
Last Updated
January 21, 2026
Results First Posted
September 23, 2025
Record last verified: 2025-09