JAK Inhibitor in Acquired Hemophagocytic synDrome in the Intensive Care Unit (JAKAHDI)

Hemophagocytic syndrome (HS) is a rare condition that can be responsible for severe organ failure. Therapeutic guidelines are mainly based on observational studies and expert opinions: no therapeutic advance has been developed for years, explaining why mortality in HS remains high (Intensive Care Unit mortality ranging from 40 to 70%). If etoposide remains the gold standard in critically ill HS patients, nearly 20% of patients are refractory to this therapy: treatment escalation is common, most often requiring the administration of intensive treatments generating high toxicity. Ruxolitinib is the first approved JAK inhibitor. It has been associated with improvement of HS manifestations and survival in a pre-clinical murine model. Data in humans are scarce but promising.

The aim is to demonstrate that ruxolitinib, in association with standard of care, may reverse organ failure (as represented by Sequential Organ Failure Assessment (SOFA) score) better than standard of care alone in critically ill patients with acquired HS.

Study Overview

• Status: Not yet recruiting
• Conditions: Hemophagocytic Syndromes
• Intervention / Treatment: Drug: Ruxolitinib

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jérôme Lambert, Pr; Phone Number: +33142499742; Email: jerome.lambert@u-paris.fr
• Study Contact Backup: Name: Sandrine Valade, Dr; Phone Number: +33142499419; Email: sandrine.valade@aphp.fr

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• adult patients older than 18 years
• acquired hemophagocytic syndrome, regardless of etiology, defined by the presence of 5 or 6 HLH-2004 criteria or HScore ≥ 200
• admission in the ICU
• need for symptomatic treatment of HS in relation with organ failure, as defined by SOFA score ≥ 4

• Informed consent signed:

  • by the patient,
  • Or informed consent signed by a family members/trustworthy person if his condition does not allow him to express his consent in written
• Or in an emergency situation and in the absence of family members/trustworthy person, the patient can be enrolled. The consent to participate to the research will be requested as soon as the condition of the patient will allow).
• The inclusion of women of childbearing potential requires the use of a highly effective contraceptive measure. Contraception should be maintained during treatment and one day after

Exclusion Criteria:

• Moribund, defined by a life expectancy < 48 hours;
• Pregnant or lactating patients (women of childbearing potential must have a negative urine or blood Human Chorionic Gonadotropin pregnancy test prior to trial entry);
• No affiliation to health insurance;
• Known hypersensitivity to ruxolitinib;
• Lactose intolerance;
• Hypersensitivity to cellulose, microcrystalline; magnesium stearate; silica, colloidal anhydrous; sodium starch glycolate (Type A); povidone K30; hydroxypropylcellulose 300 to 600 cps,
• Pre-existing decisions of withholding/withdrawing care,
• History of progressive multifocal leukoencephalopathy
• Uncontrolled cutaneous cancer
• Persons under psychiatric care that would impede understanding of informed consent and optimal treatment and follow-up
• Adults subject to a legal protection measure (guardianship, curatorship and safeguard of justice)
• Patients deprived of their liberty by a judicial or administrative decision
• Participation in another interventional research

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: Interventional medicinal product	Drug: Ruxolitinib; Oral ruxolitinib twice a day (10 mg x 2 during 28 days) in association with standard of care in HS.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival with a decrease in SOFA score ≥ 3 points	Sequential Organ Failure Assessment Score varies from 0 to 4 and permit to assess organ failure. A higher score indicates better neurological function.	At day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival in HS critically ill patients		At 6 months
SOFA score	Sequential Organ Failure Assessment Score varies from 0 to 4 and permit to assess organ failure. A higher score indicates better neurological function.	At day 1
SOFA score	Sequential Organ Failure Assessment Score varies from 0 to 4 and permit to assess organ failure. A higher score indicates better neurological function.	At day 14
SOFA score	Sequential Organ Failure Assessment Score varies from 0 to 4 and permit to assess organ failure. A higher score indicates better neurological function.	At day 28
Length of stay in Intensive Care Unit	number of days in the ICU from inclusion to ICU discharge or death	Up to 6 months
Hospital length of stay	number of days in the hospital from inclusion to hospital discharge or death	Up to 6 months
Measurement of clinical and biological manifestations	Measurements of temperature, ferritin level, CD25 soluble receptor dosage, fibrinogen level, triglycerides level, haemoglobin level, white blood cells count, platelets count	At day 1
Measurement of clinical and biological manifestations	Measurements of temperature, ferritin level, CD25 soluble receptor dosage, fibrinogen level, triglycerides level, haemoglobin level, white blood cells count, platelets count	At day 7
Measurement of temperature		At day 14
Measurement of temperature		At day 28
Measurement of ferritin level		At day 14
Measurement of ferritin level		At day 28
Measurement of CD25 soluble receptor dosage		At day 14
Measurement of CD25 soluble receptor dosage		At day 28
Measurement of fibrinogen level		At day 14
Measurement of fibrinogen level		At day 28
Measurement of triglycerides level		At day 14
Measurement of triglycerides level		At day 28
Measurement of haemoglobin level		At day 14
Measurement of haemoglobin level		At day 28
Measurement of white blood cells count		At day 14
Measurement of white blood cells count		At day 28
Platelets count		At day 14
Platelets count		At day 28
Dosages of IL2, IL6, IL10, IL12, GM-CSF, IFN gamma, TNF alpha		At day 1
Dosages of IL2, IL6, IL10, IL12, GM-CSF, IFN gamma, TNF alpha		At day 7
Dosages of IL2, IL6, IL10, IL12, GM-CSF, IFN gamma, TNF alpha		At day 14
Dosages of IL2, IL6, IL10, IL12, GM-CSF, IFN gamma, TNF alpha		At day 28
Incidence of nosocomial infections (viral and bacterial)		Until day 28
Incidence of adverse event, severe adverse event	Intensity and frequency of adverse event and severe adverse event according to the CTCAE Toxicity Grading Scale for Determining The Severity of Adverse Events	Until day 28

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2024
• Primary Completion (Estimated): August 8, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: December 26, 2023
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Estimated): February 6, 2024

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Lymphatic Diseases; Disease; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Syndrome; Lymphohistiocytosis, Hemophagocytic
• Other Study ID Numbers: APHP220919

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
• product manufactured in and exported from the U.S.: No