Nivolumab in Treating Patients With Autoimmune Disorders and Advanced, Metastatic, or Unresectable Cancer

National Cancer Institute (NCI) (NIH)
Overall Status
Recruiting ID

Study Details

Study Description

Brief Summary

This phase Ib trial studies the side effects of nivolumab and to see how well it works in treating patients with autoimmune disorders and cancer that has spread to other places in the body or cannot removed by surgery. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Detailed Description

  1. To assess the overall safety, including the incidence of dose-limiting toxicity (DLT), and other toxicities associated with the use of the anti-programmed death 1 (PD-1) antibody nivolumab in patients with varying severity of dermatomyositis (DM)/systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), inflammatory bowel disease (IBD) (ulcerative colitis [UC] and Crohn's disease [CD]), multiple sclerosis (MS), Sjogren's syndrome [SjS], and other autoimmune diseases.
  1. To evaluate the efficacy of nivolumab in terms of objective response rates (ORRs), progression-free survival (PFS), and overall survival (OS) in patients with cancer and DM/SSc, RA, SLE, IBD (UC and CD), MS, SjS, and other autoimmune diseases.

  2. To observe and record anti-tumor activity. III. To propose dosing recommendations for anti-PD-1 antibodies based on the severity of the autoimmune disorder.

  3. To evaluate the impact of nivolumab on the disease severity indices for: DM/SSc, RA, SLE, IBD: UC and CD, not specified (NS), MS.

  4. To perform molecular profiling assays on malignant and normal tissues, including, but not limited to, ribonucleic acid (RNA) sequencing, in order to: identify potential predictive and prognostic biomarkers beyond any genomic alteration by which treatment may be assigned, and identify resistance mechanisms using genomic deoxyribonucleic acid (DNA)- and ribonucleic acid (RNA)-based assessment platforms.


Patients receive nivolumab intravenously (IV) over 30 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 100 days.

Study Design

Study Type:
Anticipated Enrollment :
312 participants
Intervention Model:
Single Group Assignment
None (Open Label)
Primary Purpose:
Official Title:
A Phase Ib Study of Nivolumab in Patients With Autoimmune Disorders and Advanced Malignancies (AIM-NIVO)
Actual Study Start Date :
Apr 4, 2019
Anticipated Primary Completion Date :
Aug 31, 2022
Anticipated Study Completion Date :
Aug 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (nivolumab)

Patients receive nivolumab IV over 30 minutes every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity.

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • CMAB819
  • MDX-1106
  • NIVO
  • Nivolumab Biosimilar CMAB819
  • ONO-4538
  • Opdivo
  • Outcome Measures

    Primary Outcome Measures

    1. Incidence of adverse events [Up to 100 days]

      Will be reported overall and by severity, and dose limiting toxicities will be summarized for all patients and by disease severity cohort.

    2. Change in disease assessments [Baseline up to 100 days]

      Will be summarized at each time point for each disease severity cohort.

    3. Overall response rate [Up to 100 days]

      Will be computed along with its associated exact 95% confidence interval for all patients and by disease severity cohort.

    4. Changes in serum chemokines and circulating immune cells over time [Baseline up to 100 days]

      Will be summarized and assessed using generalized linear mixed modeling.

    5. Gene expression in normal tissues [Up to 100 days]

      Will be compared with gene expression in malignant tissues based on two-sample t-test and Wilcoxon rank sum test. False discovery rate, if appropriate, will be used to control for multiple testing.

    6. Clinical measures of interest [Up to 100 days]

      The association between demographic and clinical measures of interest with overall response rate and toxicity will be evaluated using logistic regression modeling to identify potential predictors of outcomes.

    Eligibility Criteria


    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    Inclusion Criteria:
    • Patients must have histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable. Eligible tumor types include solid tumors and malignancies in which there is known evidence of clinical activity for single agent PD-1 or PD-L1 antibodies. Nivolumab is Food and Drug Administration (FDA)-approved for the treatment of melanoma, non-small cell lung cancer (NSCLC), Merkel cell cancer, bladder cancer, renal cell carcinoma (RCC), gastric cancer, hepatocellular carcinoma (HCC), cervical cancer, head and neck cancer, Hodgkin lymphoma (HL), metastatic small cell lung cancer (SCLC), and any solid tumor with microsatellite instability (MSI)-high status confirmed. Patients with HL are eligible but must follow standard response criteria. Additional tumor types may be eligible on a case by case basis upon discussion with principal investigator (PI)

    • Patients who have previously received other forms of immunotherapy (high-dose [HD] IL-2, IFN, CTLA-4) are allowed. Patients must not have received cytokine immunotherapy for at least 4 weeks before nivolumab administration. Patients who have received prior anti-CTLA4 will be allowed and the washout period is 6 weeks

    • Age >= 18 years; children are excluded from this study but may be eligible for future pediatric phase 1 combination trials

    • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Karnofsky >=

    • Life expectancy of greater than 12 weeks

    • Leukocytes >= 2,000/mcL

    • Absolute neutrophil count >= 1,500/mcL

    • Platelets >= 100,000/mcL

    • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)

    • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN unless the patient has dermatomyositis and in the opinion of the investigator the elevation is due to diabetes mellitus (DM)

    • Creatinine ULN OR glomerular filtration rate (GFR) >= 30 mL/min (if using the Cockcroft-Gault formula)

    • Human immunodeficiency virus (HIV)-infected patients on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial

    • If evidence of chronic hepatitis B virus (HBV) infection, HBV viral load must be undetectable on suppressive therapy if indicated

    • If history of hepatitis C virus (HCV) infection, must be treated with undetectable HCV viral load

    • Patients with treated brain metastases are eligible if there is no evidence of progression for at least 4 weeks after central nervous system (CNS)-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) during the screening period. Patients with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required for at least 4 weeks (or scheduled assessment after the first cycle of treatment), and a risk-benefit analysis (discussion) by the patient and the investigator favors participation in the clinical trial

    • The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 5 months after the last dose of investigational product. Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception for a period of 7 months after the last dose of investigational product. Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab. Women must not be breastfeeding. Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile as well as azoospermic men) do not require contraception. WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over 45 in the absence of other biological or physiological causes. In addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level less than 40 mIU/mL. These durations have been calculated using the upper limit of the half-life for nivolumab (25 days) and are based on the protocol requirement that WOCBP use contraception for 5 half-lives plus 30 days, and men who are sexually active with WOCBP use contraception for 5 half-lives plus 90 days. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she (or the participating partner) should inform the treating physician immediately

    • Ability to understand and the willingness to sign a written informed consent document

    Exclusion Criteria:
    • Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events (AEs) due to agents administered more than 4 weeks earlier have not resolved or stabilized. Palliative (limited-field) radiation therapy (RT) is permitted, 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

    • Patients with prior therapy with an anti-PD-1 or anti-PD-L1

    • Patients with prior allogeneic hematologic transplant

    • Patients who are receiving any other investigational agents

    • 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

    • Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, gastrointestinal (GI) bleeding, 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. For the IBD (UC and CD) cohort, an endoscopic assessment, disease activity index, and disease specific inclusion/exclusion criteria will substitute for these factors in determining eligibility with the exception of abdominal carcinomatosis, which should prompt further evaluation

    Contacts and Locations


    Site City State Country Postal Code
    1 University of Alabama at Birmingham Cancer Center Birmingham Alabama United States 35233
    2 Stanford Cancer Institute Palo Alto Palo Alto California United States 94304
    3 University of California Davis Comprehensive Cancer Center Sacramento California United States 95817
    4 Smilow Cancer Center/Yale-New Haven Hospital New Haven Connecticut United States 06510
    5 Yale University New Haven Connecticut United States 06520
    6 Emory University Hospital/Winship Cancer Institute Atlanta Georgia United States 30322
    7 Northwestern University Chicago Illinois United States 60611
    8 University of Kansas Clinical Research Center Fairway Kansas United States 66205
    9 HaysMed University of Kansas Health System Hays Kansas United States 67601
    10 University of Kansas Cancer Center Kansas City Kansas United States 66160
    11 Lawrence Memorial Hospital Lawrence Kansas United States 66044
    12 Olathe Health Cancer Center Olathe Kansas United States 66061
    13 University of Kansas Cancer Center-Overland Park Overland Park Kansas United States 66210
    14 University of Kansas Hospital-Indian Creek Campus Overland Park Kansas United States 66211
    15 Ascension Via Christi - Pittsburg Pittsburg Kansas United States 66762
    16 Salina Regional Health Center Salina Kansas United States 67401
    17 University of Kansas Health System Saint Francis Campus Topeka Kansas United States 66606
    18 University of Kansas Hospital-Westwood Cancer Center Westwood Kansas United States 66205
    19 Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland United States 21287
    20 National Cancer Institute Developmental Therapeutics Clinic Bethesda Maryland United States 20892
    21 National Institutes of Health Clinical Center Bethesda Maryland United States 20892
    22 Massachusetts General Hospital Cancer Center Boston Massachusetts United States 02114
    23 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
    24 Wayne State University/Karmanos Cancer Institute Detroit Michigan United States 48201
    25 Siteman Cancer Center at West County Hospital Creve Coeur Missouri United States 63141
    26 Truman Medical Centers Kansas City Missouri United States 64108
    27 University of Kansas Cancer Center - North Kansas City Missouri United States 64154
    28 University of Kansas Cancer Center - Lee's Summit Lee's Summit Missouri United States 64064
    29 University of Kansas Cancer Center at North Kansas City Hospital North Kansas City Missouri United States 64116
    30 Washington University School of Medicine Saint Louis Missouri United States 63110
    31 Siteman Cancer Center-South County Saint Louis Missouri United States 63129
    32 Siteman Cancer Center at Christian Hospital Saint Louis Missouri United States 63136
    33 Siteman Cancer Center at Saint Peters Hospital Saint Peters Missouri United States 63376
    34 Roswell Park Cancer Institute Buffalo New York United States 14263
    35 NYU Winthrop Hospital Mineola New York United States 11501
    36 Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York United States 10016
    37 NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center New York New York United States 10032
    38 NYP/Weill Cornell Medical Center New York New York United States 10065
    39 Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210
    40 Thomas Jefferson University Hospital Philadelphia Pennsylvania United States 19107
    41 UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas United States 75390
    42 UT Southwestern/Simmons Cancer Center-Fort Worth Fort Worth Texas United States 76104
    43 M D Anderson Cancer Center Houston Texas United States 77030
    44 UT Southwestern Clinical Center at Richardson/Plano Richardson Texas United States 75080
    45 Huntsman Cancer Institute/University of Utah Salt Lake City Utah United States 84112
    46 Virginia Commonwealth University/Massey Cancer Center Richmond Virginia United States 23298
    47 University Health Network-Princess Margaret Hospital Toronto Ontario Canada M5G 2M9

    Sponsors and Collaborators

    • National Cancer Institute (NCI)


    • Principal Investigator: Hussein A Tawbi, University of Texas MD Anderson Cancer Center LAO

    Study Documents (Full-Text)

    None provided.

    More Information


    None provided.
    Responsible Party:
    National Cancer Institute (NCI) Identifier:
    Other Study ID Numbers:
    • NCI-2019-00241
    • NCI-2019-00241
    • 10204
    • 10204
    • UM1CA186688
    First Posted:
    Jan 25, 2019
    Last Update Posted:
    Aug 24, 2022
    Last Verified:
    Apr 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Plan to Share IPD:
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 24, 2022