Dose-modified Emapalumab and Ruxolitinib (E-Ru) Regimens for Hemophagocytic Lymphohistiocytosis

Official title

A Multiple Center, Prospective, Single Arm, Phase III Clinical Study to Evaluate the Efficacy and Safety of Dose-modified Emapalumab and Ruxolitinib in the Treatment of Hemophagocytic Lymphohistiocytosis

Overview

This study is trying to evaluate the efficacy and safety of dose-modified Emapalumab and Ruxolitinib (E-Ru) regimens for the treatment of active hemophagocytic lymphohistiocytosis.

Detailed description

This clinical trial is designed to evaluate a new treatment strategy for patients with active Hemophagocytic Lymphohistiocytosis (HLH)-a rare but severe immune disorder characterized by excessive inflammation and immune system activation. HLH can be life-threatening if not treated effectively.

The study is prospective and multicenter, meaning it will be conducted at multiple hospitals and medical institutions, and patients will be followed over time to assess treatment outcomes.

We aim to test the combination of two medications:

1. Emapalumab, a monoclonal antibody that blocks interferon-gamma, a key driver of the overactive immune response seen in HLH. In this trial, it will be used at a lower-than-standard dose to reduce potential side effects. 2. Ruxolitinib, a JAK1/2 inhibitor that can reduce inflammation by interfering with immune signaling pathways. It will be administered at a higher-than-standard dose to enhance its therapeutic effects.

Interventions

• Drug dose-modified E-Ru
  Emapalumab (1-2 mg/kg intravenously once weekly for 8 weeks) + Ruxolitinib (15-30 mg orally twice daily for 8 weeks)
• Other Salvage treatment and follow-up
  1\) for patients who did not respond to the E-Ru regimen after 7 days or who relapsed at any point during treatment, a rescue regimen such as HLH-94 or doxorubicin-etoposide-methylprednisolone (DEP) was administered; 2) for patients diagnosed with lymphoma after enrollment, chemotherapy was initiated; 3) for patients who completed 8 weeks of treatment without recurrence and had no detected HLH-related gene mutations, follow-up was initiated; and 4) for patients who met the criteria for allo-HSCT

Primary outcome measures

• 60-days OS [Time frame: 60 days]

Secondary outcome measures (5)

• Response rate [Time frame: 7, 14, 28, and 56 days]
• Security [Time frame: 7, 14, 28, and 56 days]
• EFS [Time frame: 6 months]
• Overall survival [Time frame: 6 months]
• Trend of related indicators [Time frame: 7, 14, 28, and 56 days]

Eligibility criteria

Inclusion criteria

• Fulfillment of at least five of the eight HLH-2004 criteria for HLH;
• Age 1-70 years old;
• No prior chemotherapy for HLH;
• Confirmed not pregnant and willing to use effective contraceptive measures during the study period, with the last dose of medication administered at least 12 months prior;
• Signed informed consent prior to study participation.

Exclusion criteria

• According to the New York Heart Association (NYHA) score, patients with heart disease of grade II or above (including grade II);
• HIV-infected patients;
• Patients with severe renal dysfunction (glomerular filtration rate <15 mL/min);
• Patients with severe liver cirrhosis (MELD score>20);
• Uncontrollable infections (including lung infections, intestinal infections, etc.);
• Have serious mental illness;
• Have a history of active tumor;
• Participate in other clinical investigators at the same time;
• People with central nervous system involvement;
• Exclusion criteria related to concomitant medication.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Soochow University — Suzhou

Identifiers

NCT: NCT06951971 · E-Ru

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗