The Efficacy and Safety of Corticosteroids in Combination With Ruxolitinib in the Management of Checkpoint Inhibitor Pneumonia

Study Overview
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Brief Summary
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This study is a prospective multicenter randomized controlled Interventional study, to assess the clinical efficacy and safety of corticosteroids compared to corticosteroids in combination with Ruxolitinib in the treatment of severe checkpoint inhibitor pneumonitis.

Official Title
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The Efficacy and Safety of Corticosteroids in Combination With Biological Agents in the Management of Severe Immune Related Adverse Events Cohort A: The Efficacy and Safety of Corticosteroids or Corticosteroids Combination With Ruxolitinib in Patients With Severe Checkpoint Inhibitor Pneumonia

Conditions
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Severe Checkpoint Inhibitor Pneumonitis

Intervention / Treatment
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* Drug: Corticosteroids
* Drug: Corticosteroids and Ruxolitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years old≤ Aged ≤75 years old. Diagnosis of malignancy. Malignant tumors initially treated with anti-PD-1 in combination with or without chemotherapy. Diagnosis of grade 3 or 4 CIP: CIP severity at CTCAE grade 3 or 4. Patients who and whose family members understand the study protocol, are willing to participate in the study and could provide written informed consent. Exclusion Criteria: Predicted life expectancy<12 weeks. Any evidence of active or uncontrolled viral infection, including hepatitis B, hepatitis C and human immunodeficiency virus (HIV), or any clinical signs of bacterial, other viral, parasitic or fungal infection requiring treatment. malignancy progression. Patients with other serious complications that may affect safety or adherence judged by the investigator. Any significant clinical and laboratory abnormalities judged by investigator that affect the safety evaluation. Patients can't fully understand the study protocol, arrangement and other study-related elements. Patients with evidence of severe liver or kidney dysfunction judged by investigator unsuitable for enrolment. Women who are pregnant, breast feeding or unable to use effective contraception during the study period and for 3 months after the completion. Patients who cannot comply with study treatment and follow-up according to the trial protocol.

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Cohort 1: severe CIP with the treatment of corticosteroids<br>severe CIP with the treatment of corticosteroids | Drug: Corticosteroids<br>* Initial dosage of corticosteroids is more than predinisone 1mg/kg/d or other corticosteroids with equal equivalence<br>|
| Experimental: Cohort 2: severe CIP with the treatment of corticosteroids and Ruxolitinib<br>severe CIP with the treatment of corticosteroids and Ruxolitinib | Drug: Corticosteroids and Ruxolitinib<br>* Initial dosage of corticosteroids is more than predinisone 1mg/kg/d or other corticosteroids with equal equivalence, add-on oral Ruxolitinib 5mg twice a day for 2 weeks, following with Ruxolitinib<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with dosage of corticosteroids less than 10mg daily at improvement to CIP with CTCAE grade 1. | Proportion of patients with dosage of corticosteroids less than 10mg daily at improvement to CIP with CTCAE grade 1. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | Mortality of severe CIP patients at 8 weeks. | 8 weeks | 
| Proportion of invasive ventilator assisted respiration | Proportion of invasive ventilator assisted respiration treatment for severe CIP patients at 8 weeks. | 8 weeks | 
| Incidence of pulmonary infection | Incidence of pulmonary infection in severe CIP patients in 8 weeks. | 8 weeks | 
| Total corticosteroids usage | Total corticosteroids usage for severe CIP patients in 8 weeks. | 8 weeks. | 
| The incidence of treatment with immunosuppressants and the incidence of treatment with IVIG | The incidence of treatment with immunosuppressants and the incidence of treatment with IVIG for severe CIP patients in 8 weeks. | 8 weeks. |