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

NCT ID: NCT04438382

Last Updated: 2024-06-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-07
• Study Completion Date: 2023-12-21

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.

Detailed Description

PRIMARY OBJECTIVE:

I. To assess pneumonitis response to additional immunosuppression (infliximab or intravenous immunoglobulin therapy [IVIG]) in patients with steroid-refractory pneumonitis at 28-days.

SECONDARY OBJECTIVES:

I. To assess functional parameters of steroid-refractory pneumonitis at day 1, 14-days and 28-days after day 1 of receipt of additional immunosuppression (infliximab or IVIG).

II. To assess radiologic parameters of steroid-refractory pneumonitis at day 1, 14-days and 28-days after day 1 of receipt of additional immunosuppression (infliximab or IVIG).

III. To assess patient-reported outcomes of steroid-refractory pneumonitis at day 1, 14-days and 28-days after day 1 of receipt of additional immunosuppression (infliximab or IVIG).

IV. To assess death after additional immunosuppression. V. To assess the rate of infections in the 28-day period after additional immunosuppression.

EXPLORATORY OBJECTIVES:

I. To examine lung tissue, bronchoalveolar lavage (BAL) and serial blood samples in patients who develop steroid-refractory pneumonitis.

II. To examine associations between BAL phenotypes and pneumonitis response, functional and radiologic parameters of pneumonitis.

III. To evaluate associations between pneumonitis and autoantibodies, T-cell expansion, and baseline cytokines in the blood.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive infliximab intravenously (IV) on day 1 followed by prednisone taper IV or orally (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.

ARM B: 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.

After completion of study treatment, patients are followed up at 28, 42 and 56 days.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A (infliximab)

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.

Group Type: EXPERIMENTAL

Infliximab

Intervention Type: BIOLOGICAL

Given IV

Prednisone

Intervention Type: DRUG

Given IV or PO

Methylprednisolone

Intervention Type: DRUG

Given IV or PO

Arm B (intravenous immunoglobulin therapy)

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.

Group Type: EXPERIMENTAL

Intravenous Immunoglobulin Therapy

Intervention Type: BIOLOGICAL

Given IV

Prednisone

Intervention Type: DRUG

Given IV or PO

Methylprednisolone

Intervention Type: DRUG

Given IV or PO

Interventions

Infliximab

Given IV

Intervention Type: BIOLOGICAL

Intravenous Immunoglobulin Therapy

Given IV

Intervention Type: BIOLOGICAL

Prednisone

Given IV or PO

Intervention Type: DRUG

Methylprednisolone

Given IV or PO

Intervention Type: DRUG

Other Intervention Names

Remicade; Gamma Globulin; Gamma Globulin Therapy; Immune Globulin; Immune Globulin Therapy; Intravenous Immunoglobulin; IVIG; Deltasone; Orasone; Meticorten; Panasol-S; Liquid-Pred; Methylprednisolone sodium succinate (Solu-Medrol); methylprednisolone acetate (Depo-Medrol); Methylprednisolone (Medrol)

Eligibility Criteria

Inclusion Criteria

• 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 pathogen-negative infectious diagnostic evaluation within 14 days prior to randomization, and at a minimum these should include: blood culture, urine culture, sputum culture, and viral panel: rapid flu, respiratory syncytial virus (RSV), herpes simplex virus (HSV). Empiric antibiotics for culture negative infections are not an exclusion for study entry
• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

ECOG-ACRIN Cancer Research Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jarushka Naidoo

Role: PRINCIPAL_INVESTIGATOR

ECOG-ACRIN Cancer Research Group

Locations

Northwestern University

Chicago, Illinois, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Bronson Battle Creek

Battle Creek, Michigan, United States

Mercy Health Saint Mary's

Grand Rapids, Michigan, United States

Spectrum Health at Butterworth Campus

Grand Rapids, Michigan, United States

West Michigan Cancer Center

Kalamazoo, Michigan, United States

Mercy Health Mercy Campus

Muskegon, Michigan, United States

Lakeland Hospital Niles

Niles, Michigan, United States

Cancer and Hematology Centers of Western Michigan - Norton Shores

Norton Shores, Michigan, United States

Spectrum Health Reed City Hospital

Reed City, Michigan, United States

Lakeland Medical Center Saint Joseph

Saint Joseph, Michigan, United States

Marie Yeager Cancer Center

Saint Joseph, Michigan, United States

Munson Medical Center

Traverse City, Michigan, United States

Metro Health Hospital

Wyoming, Michigan, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

VCU Massey Cancer Center at Stony Point

Richmond, Virginia, United States

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 33568350 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2018-02825

Identifier Type: REGISTRY

Identifier Source: secondary_id

EAQ172

Identifier Type: OTHER

Identifier Source: secondary_id

EAQ172

Identifier Type: OTHER

Identifier Source: secondary_id

EAQ172

Identifier Type: OTHER

Identifier Source: secondary_id

UG1CA189828

Identifier Type: NIH

Identifier Source: secondary_id

View Link

EAQ172

Identifier Type: -

Identifier Source: org_study_id