This is a multi-center, 1:1 randomized pilot study examining the efficacy and safety of infliximab 5mg/kg x 1 paired with 2 weeks of prednisone 1mg/kg per day for 2 weeks versus standard-of-care glucocorticoid therapy (prednisone 1mg/kg/day x 2 weeks followed by a 4 week taper) on the rate and speed of renal recovery from immune checkpoint inhibitor-associated AKI.
Data to guide treatment of immune-checkpoint inhibitor associated acute kidney injury (ICI-AKI) are limited, with current guidelines recommending 4-8 weeks of glucocorticoids (GCs). However, GCs have numerous side effects and can attenuate the anti-tumor response induced by ICI therapy, commonly leads to adverse events, and can delay anti-cancer therapy. Infliximab is an FDA-approved monoclonal antibody that inhibits tumor necrosis factor-α and is used to treat a variety of autoimmune diseases, as well as steroid-refractory extrarenal immune-related adverse events. A strong biologic rationale exists for its use in patients with ICI-AKI, and case reports suggest some benefit in steroid-refractory ICI-AKI; however, there are no randomized clinical trial (RCT) data to guide the upfront use of infliximab in ICI-AKI. This is a multi-center, 1:1 randomized pilot study examining the efficacy of infliximab in increasing the rate, speed, and durability of renal recovery when compared to standard of care prednisone which is current standard of care in patients receiving ICIs. The primary outcome is the rate of sustained renal recovery at 12 weeks. Key secondary outcomes include time-to-sustained renal recovery, time-to-ICI-AKI recurrence, and time-to-rechallenge with anti-cancer therapy. Additionally, we will characterize the safety profile of infliximab, as well a 6- vs. 2-week course of GCs, using the Glucocorticoid Toxicity Index.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
44
Infliximab 5mg/kg x 1 and prednisone 1mg/kg per day (rounded to the nearest 10mg) x 2 weeks
Prednisone 1mg/kg per day for 2 weeks (rounded to the nearest 10mg, maximum 100mg/day) followed by a 4-week taper, tapered by 0.2mg/kg/day per week.
Prednisone 1mg/kg per day for two weeks (Rounded do the nearest 10mg and maximum dose of 100mg per day)
Massachusetts General Hospital
Boston, Massachusetts, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Acute kidney injury recovery at 12 weeks
The proportion of patients achieving AKI recovery within 12 weeks is defined as return of serum creatinine to less than 1.5-fold baseline creatinine within the need for ongoing immunosuppression. (Active immunosuppression is defined as currently receiving \>10mg/day of prednisone equivalent or having received any non-glucocorticoid immunosuppressant within the last 2 weeks).
Time frame: 12 weeks
Time to AKI recovery
Time to AKI recovered is defined as the time in days to meeting criteria for AKI recovery as defined in the primary outcome.
Time frame: 24 weeks
Time to ICI-AKI recurrence
Time to ICI-AKI recurrence is defined as \>= 1.5-fold rise in serum creatinine compared to the lowest serum creatinine achieved while receiving immunosuppression, occurring within 24 weeks following randomization and without a clear alternative more likely cause of AKI.
Time frame: 24 weeks
Change in serum creatinine
Change from enrollment to follow-up serum creatinine
Time frame: 24 weeks
Tumor response
Tumor response is determined using the RECIST 1.1 criteria, a widely accepted 4-category scale (complete response, partial response, stable disease, and disease progression).
Time frame: 24 weeks
Progression free survival
Progression-free survival is defined as survival to 24 weeks with complete response, partial response, or stable disease
Time frame: 24 weeks
Overall survival
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Overall survival at 24 weeks
Time frame: 24 weeks
Adverse events leading to treatment discontinuation
Summary of any adverse event that leads to treatment discontinuation
Time frame: 6 weeks
Adverse events of special interest
Adverse events of infliximab inclusion infusion reaction, serious infection, headach, hepatotoxicity, serum sickness, autoimmune phenomenon, rash, new malignancy, congestive heart failure, neurotoxicity.
Time frame: 30 days after completing study treatment
Serious adverse events (SAE)
An SAE is defined as an adverse event that meets any of the following criteria 1) results in death, 2) is life threatening, 3) requires or prolongs hospitalization, 4) results in persistent or significant disability/incapacity.
Time frame: Up to 30 days after completing study treatment
Glucocorticoid toxicity index
The Glucocorticoid Toxicity Index (GTI) is a validated clinician-assessed instrument designed to prospectively quantify changes in glucocorticoid-associated morbidity over time. The GTI evaluates toxicity across multiple domains, including body mass index, glucose tolerance, blood pressure, lipid metabolism, myopathy, bone health, skin toxicity, neuropsychiatric effects, infection, ocular complications, and patient-reported symptoms. GTI will be assessed at baseline and at week 6. Higher GTI scores reflect greater glucocorticoid-associated toxicity, whereas improvements in score indicate a reduction in steroid-related adverse effects.
Time frame: 6 weeks