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

April 19, 2024 updated by: National Cancer Institute (NCI)

A Phase Ib Study of Nivolumab in Patients With Autoimmune Disorders and Advanced Malignancies (AIM-NIVO)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

300

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Recruiting
        • University Health Network-Princess Margaret Hospital
        • Contact:
        • Principal Investigator:
          • Anna Spreafico
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Active, not recruiting
        • University of Alabama at Birmingham Cancer Center
    • California
      • Palo Alto, California, United States, 94304
        • Active, not recruiting
        • Stanford Cancer Institute Palo Alto
      • Sacramento, California, United States, 95817
        • Recruiting
        • University of California Davis Comprehensive Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 916-734-3089
        • Principal Investigator:
          • Surbhi Singhal
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Recruiting
        • Yale University
        • Contact:
        • Principal Investigator:
          • Patricia M. LoRusso
      • New Haven, Connecticut, United States, 06510
        • Recruiting
        • Smilow Cancer Center/Yale-New Haven Hospital
        • Contact:
        • Principal Investigator:
          • Patricia M. LoRusso
    • District of Columbia
      • Washington, District of Columbia, United States, 20007
        • Recruiting
        • MedStar Georgetown University Hospital
        • Contact:
          • Site Public Contact
          • Phone Number: 202-444-2223
        • Principal Investigator:
          • Geoffrey T. Gibney
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Active, not recruiting
        • Emory University Hospital/Winship Cancer Institute
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Walter M. Stadler
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Contact:
        • Principal Investigator:
          • Jeffrey A. Sosman
    • Kansas
      • Fairway, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Clinical Research Center
        • Contact:
        • Principal Investigator:
          • Joaquina C. Baranda
      • Hays, Kansas, United States, 67601
        • Recruiting
        • HaysMed University of Kansas Health System
        • Contact:
          • Site Public Contact
          • Phone Number: 785-623-5774
        • Principal Investigator:
          • Joaquina C. Baranda
      • Kansas City, Kansas, United States, 66160
        • Recruiting
        • University of Kansas Cancer Center
        • Contact:
        • Principal Investigator:
          • Joaquina C. Baranda
      • Lawrence, Kansas, United States, 66044
        • Recruiting
        • Lawrence Memorial Hospital
        • Contact:
        • Principal Investigator:
          • Joaquina C. Baranda
      • Olathe, Kansas, United States, 66061
        • Recruiting
        • Olathe Health Cancer Center
        • Contact:
        • Principal Investigator:
          • Joaquina C. Baranda
      • Overland Park, Kansas, United States, 66211
        • Recruiting
        • University of Kansas Hospital-Indian Creek Campus
        • Contact:
        • Principal Investigator:
          • Joaquina C. Baranda
      • Overland Park, Kansas, United States, 66210
        • Recruiting
        • University of Kansas Cancer Center-Overland Park
        • Contact:
        • Principal Investigator:
          • Joaquina C. Baranda
      • Pittsburg, Kansas, United States, 66762
        • Recruiting
        • Ascension Via Christi - Pittsburg
        • Contact:
        • Principal Investigator:
          • Joaquina C. Baranda
      • Salina, Kansas, United States, 67401
        • Recruiting
        • Salina Regional Health Center
        • Contact:
        • Principal Investigator:
          • Joaquina C. Baranda
      • Topeka, Kansas, United States, 66606
        • Recruiting
        • University of Kansas Health System Saint Francis Campus
        • Contact:
          • Site Public Contact
          • Phone Number: 785-295-8000
        • Principal Investigator:
          • Joaquina C. Baranda
      • Westwood, Kansas, United States, 66205
        • Recruiting
        • University of Kansas Hospital-Westwood Cancer Center
        • Contact:
        • Principal Investigator:
          • Joaquina C. Baranda
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Recruiting
        • Johns Hopkins University/Sidney Kimmel Cancer Center
        • Contact:
        • Principal Investigator:
          • Julie R. Brahmer
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Institutes of Health Clinical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 800-411-1222
        • Principal Investigator:
          • A P. Chen
      • Bethesda, Maryland, United States, 20892
        • Recruiting
        • National Cancer Institute Developmental Therapeutics Clinic
        • Contact:
          • Site Public Contact
          • Phone Number: 800-411-1222
        • Principal Investigator:
          • A P. Chen
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital Cancer Center
        • Contact:
          • Site Public Contact
          • Phone Number: 877-726-5130
        • Principal Investigator:
          • Patrick A. Ott
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Contact:
          • Site Public Contact
          • Phone Number: 877-442-3324
        • Principal Investigator:
          • Patrick A. Ott
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Active, not recruiting
        • Wayne State University/Karmanos Cancer Institute
    • Missouri
      • Creve Coeur, Missouri, United States, 63141
        • Recruiting
        • Siteman Cancer Center at West County Hospital
        • Contact:
        • Principal Investigator:
          • Tanner M. Johanns
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • Truman Medical Centers
        • Contact:
          • Site Public Contact
          • Phone Number: 816-404-4375
        • Principal Investigator:
          • Joaquina C. Baranda
      • Kansas City, Missouri, United States, 64154
        • Recruiting
        • University of Kansas Cancer Center - North
        • Contact:
        • Principal Investigator:
          • Joaquina C. Baranda
      • Lee's Summit, Missouri, United States, 64064
        • Recruiting
        • University of Kansas Cancer Center - Lee's Summit
        • Contact:
        • Principal Investigator:
          • Joaquina C. Baranda
      • North Kansas City, Missouri, United States, 64116
        • Recruiting
        • University of Kansas Cancer Center at North Kansas City Hospital
        • Contact:
        • Principal Investigator:
          • Joaquina C. Baranda
      • Saint Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
        • Contact:
        • Principal Investigator:
          • Tanner M. Johanns
      • Saint Louis, Missouri, United States, 63129
        • Recruiting
        • Siteman Cancer Center-South County
        • Contact:
        • Principal Investigator:
          • Tanner M. Johanns
      • Saint Louis, Missouri, United States, 63136
        • Recruiting
        • Siteman Cancer Center at Christian Hospital
        • Contact:
        • Principal Investigator:
          • Tanner M. Johanns
      • Saint Peters, Missouri, United States, 63376
        • Recruiting
        • Siteman Cancer Center at Saint Peters Hospital
        • Contact:
        • Principal Investigator:
          • Tanner M. Johanns
    • New Jersey
      • New Brunswick, New Jersey, United States, 08903
        • Recruiting
        • Rutgers Cancer Institute of New Jersey
        • Contact:
          • Site Public Contact
          • Phone Number: 732-235-7356
        • Principal Investigator:
          • Sarah A. Weiss
    • New York
      • Mineola, New York, United States, 11501
        • Suspended
        • NYU Winthrop Hospital
      • New York, New York, United States, 10032
        • Recruiting
        • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
        • Principal Investigator:
          • Brian S. Henick
        • Contact:
      • New York, New York, United States, 10016
        • Recruiting
        • Laura and Isaac Perlmutter Cancer Center at NYU Langone
        • Contact:
        • Principal Investigator:
          • Janice M. Mehnert
      • New York, New York, United States, 10065
        • Recruiting
        • NYP/Weill Cornell Medical Center
        • Contact:
          • Site Public Contact
          • Phone Number: 212-746-1848
        • Principal Investigator:
          • Barbara T. Ma
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Ohio State University Comprehensive Cancer Center
        • Contact:
        • Principal Investigator:
          • Yuanquan Yang
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Active, not recruiting
        • Thomas Jefferson University Hospital
      • Pittsburgh, Pennsylvania, United States, 15232
        • Recruiting
        • University of Pittsburgh Cancer Institute (UPCI)
        • Principal Investigator:
          • Yana Najjar
        • Contact:
          • Site Public Contact
          • Phone Number: 412-647-8073
    • Texas
      • Dallas, Texas, United States, 75390
        • Recruiting
        • UT Southwestern/Simmons Cancer Center-Dallas
        • Contact:
        • Principal Investigator:
          • Hans Hammers
      • Dallas, Texas, United States, 75237
        • Recruiting
        • UT Southwestern Simmons Cancer Center - RedBird
        • Contact:
        • Principal Investigator:
          • Hans Hammers
      • Fort Worth, Texas, United States, 76104
        • Recruiting
        • UT Southwestern/Simmons Cancer Center-Fort Worth
        • Contact:
        • Principal Investigator:
          • Hans Hammers
      • Houston, Texas, United States, 77030
        • Recruiting
        • M D Anderson Cancer Center
        • Contact:
        • Principal Investigator:
          • Ecaterina E. Ileana Dumbrava
      • Richardson, Texas, United States, 75080
        • Recruiting
        • UT Southwestern Clinical Center at Richardson/Plano
        • Contact:
        • Principal Investigator:
          • Hans Hammers
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Active, not recruiting
        • Huntsman Cancer Institute/University of Utah
    • Virginia
      • Richmond, Virginia, United States, 23298
        • Recruiting
        • Virginia Commonwealth University/Massey Cancer Center
        • Contact:
        • Principal Investigator:
          • Andrew Poklepovic

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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. Patients also undergo collection of blood, CSF, tissue, stool, and urine samples throughout the trial.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • CMAB819
  • Nivolumab Biosimilar CMAB819
  • ABP 206
  • Nivolumab Biosimilar ABP 206
  • BCD-263
  • Nivolumab Biosimilar BCD-263
Procedure: Biospecimen Collection
Undergo collection of blood, CSF, tissue, stool and urine samples
Other Names:
  • Biological Sample Collection
  • Biospecimen Collected
  • Specimen Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events
Time Frame: 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.
Up to 100 days
Change in disease assessments
Time Frame: Baseline up to 100 days
Will be summarized at each time point for each disease severity cohort.
Baseline up to 100 days
Overall response rate
Time Frame: Up to 100 days
Will be computed along with its associated exact 95% confidence interval for all patients and by disease severity cohort.
Up to 100 days
Changes in serum chemokines and circulating immune cells over time
Time Frame: Baseline up to 100 days
Will be summarized and assessed using generalized linear mixed modeling.
Baseline up to 100 days
Gene expression in normal tissues
Time Frame: 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.
Up to 100 days
Clinical measures of interest
Time Frame: 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.
Up to 100 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Cancer Institute (NCI)

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 16, 2019

Primary Completion (Estimated)

August 31, 2024

Study Completion (Estimated)

August 31, 2024

Study Registration Dates

First Submitted

January 24, 2019

First Submitted That Met QC Criteria

January 24, 2019

First Posted (Actual)

January 25, 2019

Study Record Updates

Last Update Posted (Actual)

April 22, 2024

Last Update Submitted That Met QC Criteria

April 19, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2019-00241 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • UM1CA186688 (U.S. NIH Grant/Contract)
  • 10204 (Other Identifier: CTEP)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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