Treatment Efficacy of Corticosteroids and Mycophenolate Mofetil in Patients With Immune Related Hepatitis

Phase

Condition

Hepatitis

Liver Disorders

Treatment

N/A

Clinical Study ID

NCT04810156

AA2032

Ages > 18
All Genders

Study Summary

This clinical trial is to clarify and investigate the patterns of immune-related hepatitis and the optimal treatment choice for patients who are steroid-dependent. The project aims to prospectively characterize the various histopathological, biochemical, and phenotypical liver injury patterns induced by immune checkpoint inhibitors and the treatment responses to corticosteroids. Furthermore, the effect of adding a second-line immunosuppressive drug, either MMF in steroid-refractory or steroid-dependent cases will be explored and compared.

Eligibility Criteria

Inclusion

Inclusion Criteria: Cohort A:

Abnormal liver parameters equal to ≥ grade 3 ir-hepatitis defined as; AST/ALT/ALP >5 xULN, INR ≥ 2.5 x ULN, or bilirubin > 3.0 x ULN Cohort B:
Patients who recur during or within one months of prednisolone tapering of ≥2ir-hepatitis equal to AST/ALT ≥3 x ULN, ALP ≥2.5 x ULN, INR ≥ 1.5 x ULN, or bilirubin ≥ 3.0x ULN Cohort A and Cohort B
Histologically confirmed solid cancer
Treatment with cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) or Programmed CellDeath-1 (PD-1)/Programmed Cell Death Ligand-1 (PD-L1) inhibitor or a combination ofCTLA-4 plus PD-1 inhibitors within 6 months
Age: ≥ 18 years
Women of childbearing potential: Negative serum pregnancy test and must use effectivecontraception. This applies from screening and until 6 months after treatment. Birthcontrol pills, spiral, depot injection with gestagen, subdermal implantation, hormonalvaginal ring and transdermal depot patch are all considered effective contraceptives
Men with female partner of childbearing potential must use effective contraceptionfrom screening and until 6 months after treatment. Effective contraceptives are asdescribed above for the female partner. In addition, documented vasectomy andsterility or double barrier contraception are considered effective contraceptives
Signed statement of consent after receiving oral and written study information
Willingness to participate in the planned treatment and follow-up and capable ofhandling toxicities.

Exclusion

Exclusion Criteria:

Concomitant chemotherapy treatment or tyrosine kinases or angiogenesis inhibitors
Concomitant immunosuppressive medication except prednisolone
Patients with hepatocellular carcinoma
Known hypersensitivity to one of the active drugs or excipients
Uncontrolled infection
Acute viral hepatitis
Any medical condition that will interfere with patient compliance or safety
Simultaneous treatment with other experimental drugs or other anticancer drugs
Pregnant or breastfeeding females
Phenylketonuria

Study Design

April 07, 2021

November 07, 2025

Study Description

The number of patients treated with immune checkpoint inhibitors (ICI) is expanding worldwide due to an increasing number of indications, including additional types of cancer, combination of ICI with other antineoplastic therapies and have recently moved into the adjuvant setting. According to clinical trial material, almost all patients in ICI treatment will eventually develop any grade of an adverse event, here, estimated in up to 90 percent of treated patients. Around 10-30 percent of ICI-treated patients will show signs of liver injury related to ICI treatment and will be diagnosed with immune-related hepatitis. The treatment hereof should include observation and medium-dose steroids in low-grade asymptomatic patients (grade ≤ 2 ir-hepatitis) and high-dose steroids in higher grades according to the current European and American guidelines. However, up to 25 percent of patients with ir-hepatitis may not respond properly to steroids due to primary resistance or relapse during tapering. These patients should be offered a second-line immunosuppressive treatment. The present recommendation for patients with steroid-dependent ir-hepatitis is based on the case series and includes immunosuppressive treatment with mycophenolate mofetil (MMF). To date, no evidence exists for which second-line treatment to choose.

However, in the clinic, the initiation of MMF may be delayed, meanwhile, patients are typically treated with an increased dose of steroids. In some cases, an increased dose of steroids with prolonged tapering can be sufficient. We want to explore if increased doses of steroids or adding MMF is the best strategy for relapse of hepatitis.

In addition, patients with signs of biliary or mixed liver injury may benefit from adding ursodeoxycholic acid (UDCA).

Connect with a study center

Herlev University Hospital
Herlev, Copenhagen 2730
Denmark
Active - Recruiting
Aalborg University Hospital
Aalborg, 9000
Denmark
Site Not Available
Aarhus University Hospital
Aarhus, 8000
Denmark
Active - Recruiting
Rigshospitalet
Copenhagen, 2100
Denmark
Active - Recruiting
Odense University Hospital
Odense, 5000
Denmark
Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.