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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hemophagocytic Lymphohistiocytosis (HLH)
• Intervention / Treatment: Drug: dose-modified E-Ru; Other: Salvage treatment and follow-up

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Yue Song, Dr; Phone Number: +86 18810253070; Email: xueqifeng1992@163.com

Study Locations

• China
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
      • Contact: Yue Song, Dr.; Phone Number: +86 18810253070; Email: xueqifeng1992@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Fulfillment of at least five of the eight HLH-2004 criteria for HLH;
2. Age 1-70 years old;
3. No prior chemotherapy for HLH;
4. 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;
5. Signed informed consent prior to study participation.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: E-Ru for HLH; dose-modified Emapalumab+Ruxolitinib for the treatment of HLH patients.

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, allo-HSCT was performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
60-days OS	overall survival (OS) rate at 60 days (2-month OS)	60 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	The ORR was defined as the percentage of patients with a complete response (CR), a partial response (PR), or an improvement in the measures of HLH.	7, 14, 28, and 56 days
Security	Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE 5.0).	7, 14, 28, and 56 days
EFS	event-free survival, defined as the time from the first administration of E-Ru until no response on day 7, disease progression or death from any cause	6 months
Overall survival	OS (defined as the time from the first administration of E-Ru until death from any cause)	6 months
Trend of related indicators	Changes in biomarkers between baseline and post-treatment.	7, 14, 28, and 56 days

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital of Soochow University
• Investigators: Principal Investigator: Xuefeng He, Dr., The First Affiliated Hospital of Soochow University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2025
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: April 23, 2025
• First Submitted That Met QC Criteria: April 23, 2025
• First Posted (Actual): April 30, 2025

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Lymphatic Diseases; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphohistiocytosis, Hemophagocytic
• Other Study ID Numbers: E-Ru

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No