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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1
Given IV
Given IV
Given IV or PO
Given IV or PO
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
...and 8 more locations
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.
Time frame: At day 28
Proportion of Patients With Radiologic Response for Steroid-refractory Pneumonitis
Radiologic features of steroid-refractory pneumonitis will be assessed by percentage lung parenchyma involved, percentage of ground-glass opacity in lung parenchyma, and lung volume on computed tomography. The pneumonitis and lung volume will be graded "Definitely decreased", "Probably decreased", "No significant change", "Probably increased" and "Definitely increased". Response to study therapy will be defined by combining the categories "Definitely decreased" and "Probably decreased".
Time frame: At days 1, 14, and 28
Functional Parameters of Steroid-refractory Pneumonitis by Spirometry
Functional features of pneumonitis will be assessed by spirometry (forced vital capacity, forced expiratory volume in one second). These quantitative measures will be reported descriptively (by median, mean, and range) by timepoints and treatment arms.
Time frame: At days 1, 14, and 28
Functional Parameters of Steroid-refractory Pneumonitis by Diffusion Capacity
Functional features of pneumonitis will be assessed by diffusion capacity of the lung. These quantitative measures will be reported descriptively (by median, mean, and range) by timepoints and treatment arms.
Time frame: At days 1, 14, and 28
Functional Parameters of Steroid-refractory Pneumonitis by Oxygen Saturation
Functional features of pneumonitis will be assessed by oxygen saturation on room air at rest, collected as part of the vital signs. These quantitative measures will be reported descriptively (by median, mean, and range) by timepoints and treatment arms.
Time frame: At days 1, 14, and 28
Number of Deaths Within 28 Days
Death reported in the 28-day period will be tabulated by treatment arm, and classified as pneumonitis-related, immunosuppression related, disease-related or other.
Time frame: Up to 28 days
Incidence of Adverse Events
Will be graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The number and severity of treatment-related adverse events from infections in any organ system by the CTCAE reported in the 28-day period after additional immunosuppression.
Time frame: Up to 28 days
Total Score of Functional Assessment of Cancer Therapy - Lung Version 4
Patient-reported outcomes of steroid-refractory pneumonitis will be measured by questionnaires (Functional Assessment of Cancer Therapy - Lung version 4 \[FACT-L\]). FACT-L consists of 5 subscales and the total score is calculated by summing the scores of the 36 items. The score ranges between 0 and 136. The higher the score, the better the quality of life.
Time frame: At days 1, 14, and 28
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