Infliximab and Intravenous Immunoglobulin Therapy in Treating Patients With Steroid-Refractory Pneumonitis

NCT04438382 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: EAQ172NCI-2018-02825UG1CA189828
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 18

Brief Summary

This phase II trial studies how well infliximab and intravenous immunoglobulin therapy work in treating patients with pneumonitis that does not respond to steroid treatment. Immunotherapy with monoclonal antibodies such as, infliximab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Intravenous immunoglobulin therapy may improve pneumonitis. It is not yet known whether giving infliximab and intravenous immunoglobulin therapy will work better in treating patients with pneumonitis.

Conditions

Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm; Steroid-Refractory Pneumonitis

Outcome Measures

Primary Outcomes (1)

• Pneumonitis Response Rate

  Pneumonitis response will be defined as an improvement in partial pressure of arterial oxygen (PaO2)/fraction of inspired oxygen (FiO2) of \>= 20% measured by PaO2 and recording of the FiO2 received by the patient at the time of the arterial blood gas assessment, on day 28 compared with day 1.

  At day 28

Secondary Outcomes (7)

• Proportion of Patients With Radiologic Response for Steroid-refractory Pneumonitis

  At days 1, 14, and 28

• Functional Parameters of Steroid-refractory Pneumonitis by Spirometry

  At days 1, 14, and 28

• Functional Parameters of Steroid-refractory Pneumonitis by Diffusion Capacity

  At days 1, 14, and 28

• Functional Parameters of Steroid-refractory Pneumonitis by Oxygen Saturation

  At days 1, 14, and 28

• Number of Deaths Within 28 Days

  Up to 28 days

Other Outcomes (2)

• Distribution of Biomarkers in Patients Who Develop Steroid-refractory Pneumonitis

  Days 1, 14 and 28 after study treatment

• To Evaluate Associations Between Pneumonitis and Autoantibodies, T Cell Expansion, and Baseline Cytokines in the Blood

  On days 1, 14, and 28 post-treatment

Study Arms (2)

Arm A (infliximab)

EXPERIMENTAL

Patients receive infliximab IV on day 1 followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Patients may receive an additional dose of infliximab IV on day 14 at the discretion of the treating physician.

Biological: Infliximab; Drug: Prednisone; Drug: Methylprednisolone

Arm B (intravenous immunoglobulin therapy)

EXPERIMENTAL

Patients receive intravenous immunoglobulin therapy IV over 2-5 days per institutional guidelines followed by prednisone taper IV or PO for 4-6 weeks in the absence of disease progression or unacceptable toxicity.

Biological: Intravenous Immunoglobulin Therapy; Drug: Prednisone; Drug: Methylprednisolone

Interventions

Infliximab BIOLOGICAL

Given IV

Also known as: Remicade

Arm A (infliximab)

Intravenous Immunoglobulin Therapy BIOLOGICAL

Given IV

Also known as: Gamma Globulin, Gamma Globulin Therapy, Immune Globulin, Immune Globulin Therapy, Intravenous Immunoglobulin, IVIG

Arm B (intravenous immunoglobulin therapy)

Prednisone DRUG

Given IV or PO

Also known as: Deltasone, Orasone, Meticorten, Panasol-S, Liquid-Pred

Arm A (infliximab); Arm B (intravenous immunoglobulin therapy)

Methylprednisolone DRUG

Given IV or PO

Also known as: Methylprednisolone sodium succinate (Solu-Medrol), methylprednisolone acetate (Depo-Medrol), Methylprednisolone (Medrol)

Arm A (infliximab); Arm B (intravenous immunoglobulin therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must be English-speaking and be able to provide informed consent
• Patient must be willing and able to undergo arterial blood gas assessment as per the treating investigator. Patient must not have contraindication for arterial blood gas assessment
• Women must not be pregnant or breast-feeding due to the potential risk to the fetus of infliximab or IVIG. All females of childbearing potential must have a blood test or urine test within 14 days prior to randomization to rule out pregnancy. A female of childbearing potential is any woman, regardless of sexual orientation or whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
• Women of childbearing potential and sexually active males must be strongly advised to use an accepted and effective method(s) of contraception or to abstain from sexual intercourse for a minimum of 56 days (the duration of their participation in the study)
• Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3
• Patient may have received any number of lines of prior systemic therapy
• Patient may have any solid tumor or hematologic malignancy is eligible
• Patient must have received treatment with an anti-PD-1/PD-L1 agent either alone or in combination with another anti-cancer agent, as their most recent therapy prior to development of pneumonitis
• Patient must have steroid-refractory pneumonitis defined as:
• Grade 2 pneumonitis that has not clinically improved by a Common Terminology Criteria for Adverse Events (CTCAE) grade in greater than 72 hours or maximum of 14 days or
• Grade 3 or higher pneumonitis that has not clinically improved by a CTCAE grade in greater than 48 hours or maximum of 14 days with high dose corticosteroids (methylprednisolone or prednisone 1-4 mg/kg/equivalent) as their most recent treatment for pneumonitis, as determined by the treating investigator
• Patient may have received anti-PD-1/PD-L1 therapy as standard-of-care or part of a clinical trial
• Patient must have had a pathogen-negative bronchoscopic assessment of BAL fluid within 14 days prior to randomization. A minimum assessment for pathogens on BAL must include: gram stain, fungal panel, viral panel
• Patient must have a negative tuberculosis assessment (TB spot test, quantiferon gold or tuberculin skin test) within 14 days prior to randomization
• Patient must have chest computed tomography (CT) scan without contrast performed =\< 14 days before randomization. Patient must not have a contraindication for CT

You may not qualify if:

• Patient must not have clinical evidence of cardiac dysfunction (as determined by the treating investigator) as an alternative diagnosis to steroid-refractory pneumonitis
• Patient must not be receiving anti-PD-1/-PD-L1 agent in combination with any of the following anti-cancer agents: docetaxel, cyclophosphamide, gefitinib, erlotinib, osimertinib, crizotinib, bleomycin, afatinib
• Patient must not be receiving concurrent radiation therapy to the chest
• Patient must not be deemed to have radiation pneumonitis. Patients with a history of stable radiation pneumonitis not requiring corticosteroid therapy within the last 3 months prior to randomization will be allowed on study
• Patient must not have pre-existing interstitial lung disease or pneumonitis requiring corticosteroid therapy from any other cause, as determined by the treating investigator
• Patient must not have an absolute contraindication to IVIG or infliximab, including: clinical history of severe hypersensitivity reaction, selective IgA deficiency, active hepatitis B, active tuberculosis, active human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) where a study subject has a CD4 count of =\< 200 at screening, or drug interaction

Sponsors & Collaborators

• ECOG-ACRIN Cancer Research Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (18)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Bronson Battle Creek

Battle Creek, Michigan, 49017, United States

Location

Mercy Health Saint Mary's

Grand Rapids, Michigan, 49503, United States

Location

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, 49503, United States

Location

West Michigan Cancer Center

Kalamazoo, Michigan, 49007, United States

Location

Mercy Health Mercy Campus

Muskegon, Michigan, 49444, United States

Location

Lakeland Hospital Niles

Niles, Michigan, 49120, United States

Location

Cancer and Hematology Centers of Western Michigan - Norton Shores

Norton Shores, Michigan, 49444, United States

Location

Spectrum Health Reed City Hospital

Reed City, Michigan, 49677, United States

Location

Lakeland Medical Center Saint Joseph

Saint Joseph, Michigan, 49085, United States

Location

Marie Yeager Cancer Center

Saint Joseph, Michigan, 49085, United States

Location

Munson Medical Center

Traverse City, Michigan, 49684, United States

Location

Metro Health Hospital

Wyoming, Michigan, 49519, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

VCU Massey Cancer Center at Stony Point

Richmond, Virginia, 23235, United States

Location

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

• Beattie J, Rizvi H, Fuentes P, Luo J, Schoenfeld A, Lin IH, Postow M, Callahan M, Voss MH, Shah NJ, Betof Warner A, Chawla M, Hellmann MD. Success and failure of additional immune modulators in steroid-refractory/resistant pneumonitis related to immune checkpoint blockade. J Immunother Cancer. 2021 Feb;9(2):e001884. doi: 10.1136/jitc-2020-001884.

  PMID: 33568350 DERIVED

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Infliximab; gamma-Globulins; Immunoglobulins; Immunoglobulins, Intravenous; Prednisone; Methylprednisolone; Methylprednisolone Hemisuccinate; Methylprednisolone Acetate

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin G; Immunoglobulin Isotypes; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Prednisolone; Pregnadienetriols

Limitations and Caveats

Only one patient was enrolled on this study. Due to the concern on confidentiality, individual data was not reported.

Results Point of Contact

• Title: Study Statistician
• Organization: ECOG-ACRIN Statistical Office

eatrials@jimmy.harvard.edu

617-632-3012

Study Officials

• Jarushka Naidoo

  ECOG-ACRIN Cancer Research Group

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 9, 2020
• First Posted: June 18, 2020
• Study Start: January 7, 2021
• Primary Completion: December 21, 2023
• Study Completion: December 21, 2023
• Last Updated: April 2, 2026
• Results First Posted: March 26, 2024

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (18)