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

NCT ID: NCT03816345

Last Updated: 2026-02-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-16

Study Completion Date

2028-03-30

Brief Summary

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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

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PRIMARY OBJECTIVE:

I. To assess the overall safety, and 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 \[SjS\], Psoriasis (PsO)/Psoriatic Arthritis (PsA), and other autoimmune diseases.

SECONDARY OBJECTIVES:

I. 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, PsO/PsA, and other autoimmune diseases.

II. 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.

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

V. To identify biomarkers of response and toxicity.

OUTLINE:

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. Patients also undergo collection of blood, cerebrospinal fluid (CSF), tissue, stool, and urine samples throughout the trial.

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

Conditions

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Autoimmune Disease Crohn Disease Dermatomyositis Hematopoietic and Lymphoid Cell Neoplasm Inflammatory Bowel Disease Malignant Solid Neoplasm Multiple Sclerosis Psoriasis Psoriatic Arthritis Rheumatoid Arthritis Sjogren Syndrome Systemic Lupus Erythematosus Systemic Scleroderma Ulcerative Colitis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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. Patients also undergo collection of blood, CSF, tissue, stool, and urine samples throughout the trial.

Group Type EXPERIMENTAL

Biospecimen Collection

Intervention Type PROCEDURE

Undergo collection of blood, CSF, tissue, stool and urine samples

Nivolumab

Intervention Type BIOLOGICAL

Given IV

Interventions

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Biospecimen Collection

Undergo collection of blood, CSF, tissue, stool and urine samples

Intervention Type PROCEDURE

Nivolumab

Given IV

Intervention Type BIOLOGICAL

Other Intervention Names

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Biological Sample Collection Biospecimen Collected Specimen Collection ABP 206 BCD-263 BMS 936558 BMS-936558 BMS936558 CMAB819 MDX 1106 MDX-1106 MDX1106 NIVO Nivolumab Biosimilar ABP 206 Nivolumab Biosimilar BCD-263 Nivolumab Biosimilar CMAB819 ONO 4538 ONO-4538 ONO4538 Opdivo

Eligibility Criteria

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Inclusion Criteria

* Patients can have either histologically confirmed malignancy that is radiologically evaluable and metastatic or unresectable, or have a malignancy for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting. 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 enrolling on the trial for adjuvant use will be restricted to those with histology for which a PD-1/PD-L1 inhibitor has been approved in the adjuvant setting including but not limited to NSCLC, melanoma, RCC, cervical cancer, and bladder cancer
* 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 \>= 60)
* Life expectancy of greater than 12 weeks
* Leukocytes \>= 1,000/mcL
* Absolute neutrophil count \>= 500/mcL
* Platelets \>= 50,000/mcL
* Total bilirubin =\< 2 x institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 5 x institutional ULN or =\< 8 x institutional ULN for patients with liver metastases or an autoimmune disease that is contributing to the elevation of these values
* 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 new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate central nervous system (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
* Patients with more than one autoimmune disease are eligible. The treating physician would determine which autoimmune disease is dominant and the patient would be treated under that specific cohort

Exclusion Criteria

* Patients who have had chemotherapy or radiotherapy within 2 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 (2 week washout from start of treatment), 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 anticancer 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Hussein A Tawbi

Role: PRINCIPAL_INVESTIGATOR

University of Texas MD Anderson Cancer Center LAO

Locations

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University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

Site Status ACTIVE_NOT_RECRUITING

Stanford Cancer Institute Palo Alto

Palo Alto, California, United States

Site Status ACTIVE_NOT_RECRUITING

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Site Status RECRUITING

Smilow Cancer Center/Yale-New Haven Hospital

New Haven, Connecticut, United States

Site Status RECRUITING

Yale University

New Haven, Connecticut, United States

Site Status RECRUITING

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, United States

Site Status ACTIVE_NOT_RECRUITING

Northwestern University

Chicago, Illinois, United States

Site Status ACTIVE_NOT_RECRUITING

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Site Status ACTIVE_NOT_RECRUITING

University of Kansas Clinical Research Center

Fairway, Kansas, United States

Site Status RECRUITING

HaysMed

Hays, Kansas, United States

Site Status RECRUITING

University of Kansas Cancer Center

Kansas City, Kansas, United States

Site Status RECRUITING

Lawrence Memorial Hospital

Lawrence, Kansas, United States

Site Status RECRUITING

The University of Kansas Cancer Center - Olathe

Olathe, Kansas, United States

Site Status RECRUITING

University of Kansas Cancer Center-Overland Park

Overland Park, Kansas, United States

Site Status RECRUITING

University of Kansas Hospital-Indian Creek Campus

Overland Park, Kansas, United States

Site Status RECRUITING

Mercy Hospital Pittsburg

Pittsburg, Kansas, United States

Site Status SUSPENDED

Salina Regional Health Center

Salina, Kansas, United States

Site Status RECRUITING

University of Kansas Health System Saint Francis Campus

Topeka, Kansas, United States

Site Status RECRUITING

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, United States

Site Status RECRUITING

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Site Status RECRUITING

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Site Status RECRUITING

National Cancer Institute Developmental Therapeutics Clinic

Bethesda, Maryland, United States

Site Status RECRUITING

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status ACTIVE_NOT_RECRUITING

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Site Status ACTIVE_NOT_RECRUITING

Siteman Cancer Center at Saint Peters Hospital

City of Saint Peters, Missouri, United States

Site Status RECRUITING

Siteman Cancer Center at West County Hospital

Creve Coeur, Missouri, United States

Site Status RECRUITING

University Health Truman Medical Center

Kansas City, Missouri, United States

Site Status RECRUITING

University of Kansas Cancer Center - North

Kansas City, Missouri, United States

Site Status RECRUITING

University of Kansas Cancer Center - Lee's Summit

Lee's Summit, Missouri, United States

Site Status RECRUITING

University of Kansas Cancer Center at North Kansas City Hospital

North Kansas City, Missouri, United States

Site Status RECRUITING

Washington University School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Siteman Cancer Center-South County

St Louis, Missouri, United States

Site Status RECRUITING

Siteman Cancer Center at Christian Hospital

St Louis, Missouri, United States

Site Status RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status RECRUITING

NYU Langone Hospital - Long Island

Mineola, New York, United States

Site Status RECRUITING

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Site Status RECRUITING

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States

Site Status RECRUITING

NYP/Weill Cornell Medical Center

New York, New York, United States

Site Status RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status RECRUITING

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status ACTIVE_NOT_RECRUITING

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

UT Southwestern Simmons Cancer Center - RedBird

Dallas, Texas, United States

Site Status RECRUITING

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Site Status RECRUITING

UT Southwestern/Simmons Cancer Center-Fort Worth

Fort Worth, Texas, United States

Site Status RECRUITING

M D Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

UT Southwestern Clinical Center at Richardson/Plano

Richardson, Texas, United States

Site Status RECRUITING

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Site Status ACTIVE_NOT_RECRUITING

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, United States

Site Status RECRUITING

University Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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United States Canada

Facility Contacts

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Site Public Contact

Role: primary

916-734-3089

Site Public Contact

Role: primary

203-785-5702

Site Public Contact

Role: primary

203-785-5702

Site Public Contact

Role: primary

202-444-2223

Site Public Contact

Role: primary

913-588-3671

Site Public Contact

Role: primary

785-623-5774

Site Public Contact

Role: primary

913-588-3671

Site Public Contact

Role: primary

785-505-2800

Site Public Contact

Role: primary

913-588-1569

Site Public Contact

Role: primary

913-588-3671

Site Public Contact

Role: primary

913-588-3671

Site Public Contact

Role: primary

785-452-7038

Site Public Contact

Role: primary

785-295-8000

Site Public Contact

Role: primary

913-588-3671

Site Public Contact

Role: primary

859-257-3379

Site Public Contact

Role: primary

410-955-8804

Site Public Contact

Role: primary

800-411-1222

Site Public Contact

Role: primary

877-726-5130

Site Public Contact

Role: primary

877-442-3324

Site Public Contact

Role: primary

800-600-3606

Site Public Contact

Role: primary

800-600-3606

Site Public Contact

Role: primary

816-404-4375

Site Public Contact

Role: primary

913-588-3671

Site Public Contact

Role: primary

913-588-3671

Site Public Contact

Role: primary

913-588-3671

Site Public Contact

Role: primary

800-600-3606

Site Public Contact

Role: primary

800-600-3606

Site Public Contact

Role: primary

800-600-3606

Site Public Contact

Role: primary

732-235-7356

Site Public Contact

Role: primary

212-263-4432

Site Public Contact

Role: primary

Site Public Contact

Role: primary

212-342-5162

Site Public Contact

Role: primary

212-746-1848

Site Public Contact

Role: primary

800-293-5066

Site Public Contact

Role: primary

412-647-8073

Site Public Contact

Role: primary

214-648-7097

Site Public Contact

Role: primary

214-648-7097

Site Public Contact

Role: primary

214-648-7097

Site Public Contact

Role: primary

877-632-6789

Site Public Contact

Role: primary

972-669-7044

Site Public Contact

Role: primary

804-628-6430

Site Public Contact

Role: primary

416-946-4501

References

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Vaziri H, Turshudzhyan A, Vecchio E. Immunotherapy-induced Colitis: A Comprehensive Review of Epidemiology, Clinical Presentation, Diagnostic Workup, and Management Plan. J Clin Gastroenterol. 2022 Aug 1;56(7):555-564. doi: 10.1097/MCG.0000000000001705. Epub 2022 Apr 21.

Reference Type DERIVED
PMID: 35470301 (View on PubMed)

Other Identifiers

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NCI-2019-00241

Identifier Type: REGISTRY

Identifier Source: secondary_id

10204

Identifier Type: OTHER

Identifier Source: secondary_id

10204

Identifier Type: OTHER

Identifier Source: secondary_id

UM1CA186688

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2019-00241

Identifier Type: -

Identifier Source: org_study_id

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