Ongoing Clinical Trials for Haemophagocytic Lymphohistiocytosis
There are currently 5 clinical trials investigating new treatments for haemophagocytic lymphohistiocytosis, a severe condition where the immune system becomes overactive and attacks the body’s own tissues. These studies are testing medications such as ruxolitinib, etoposide, emapalumab, and itacitinib in patients ranging from infants to older adults. Trials are taking place in France, Italy, the Czech Republic, the Netherlands, and Guadeloupe.
Clinical trial locations
- Czechia
- France
- A study of ruxolitinib as first treatment for children with haemophagocytic lymphohistiocytosis (HLH)
- Study on Etoposide for Patients with Severe Hemophagocytic Lymphohistiocytosis in Intensive Care
- Study on Itacitinib for Treating Non-Severe Hemophagocytic Lymphohistiocytosis in Adults
- Study on Ruxolitinib and Drug Combination for Critically Ill Adults with Acquired Hemophagocytic Syndrome
- Guadeloupe
- Italy
- Netherlands
A study of ruxolitinib as first treatment for children with haemophagocytic lymphohistiocytosis (HLH)
This Phase 2 study is investigating ruxolitinib, also known as Jakavi, as a first-line treatment for children with primary haemophagocytic lymphohistiocytosis. The medication is being tested in combination with corticosteroids to help children survive until they can receive a haematopoietic stem cell transplantation, a procedure where damaged bone marrow is replaced with healthy cells.
Inclusion criteria: Children aged between 0 and 22 years with confirmed HLH syndrome may be eligible. The diagnosis must be confirmed either through genetic testing showing predisposition to primary HLH, or by meeting at least 5 specific criteria including fever, enlarged spleen, low blood cell counts in at least two types of blood cells, high levels of fats in blood or low blood clotting proteins, and other characteristic findings. Patients must not have received any previous treatment specifically for HLH syndrome, except for corticosteroids. Those who could become pregnant must agree to use effective birth control during the study and for a specified period afterward.
Exclusion criteria: Children who have already received treatment for HLH other than corticosteroids cannot participate. Other exclusion factors include severe liver dysfunction, active uncontrolled infections, history of organ transplants, known allergies to ruxolitinib or similar medications, severe heart conditions, pregnancy or breastfeeding, participation in other clinical trials, and significant kidney problems.
Study focus: The study aims to evaluate how well patients survive until they can receive stem cell transplantation. The treatment period lasts up to 8 weeks, with patients receiving daily doses of Jakavi tablets in strengths of 5 mg, 10 mg, 15 mg, or 20 mg, taken by mouth. The maximum daily dose is 100 mg.
Investigational drugs: Ruxolitinib belongs to a group of drugs called JAK inhibitors that help control the immune system’s response by reducing inflammation and controlling overactive immune responses. It is used in combination with corticosteroids, which are anti-inflammatory medications that help suppress immune system activity.
Study on Ruxolitinib and Drug Combination for Critically Ill Adults with Acquired Hemophagocytic Syndrome
This clinical trial focuses on critically ill adults admitted to the intensive care unit with acquired hemophagocytic syndrome. The study investigates whether ruxolitinib, when used alongside standard treatments, can better reverse organ failure compared to standard treatments alone.
Inclusion criteria: Adults older than 18 years with acquired hemophagocytic syndrome who are admitted to the ICU may be eligible. Patients must need treatment for organ failure as shown by a SOFA score of 4 or higher, which measures how well the organs are working. The diagnosis of hemophagocytic syndrome must meet specific criteria. Informed consent must be signed by the patient or a family member if the patient cannot sign due to their condition. Women who can have children must use highly effective contraception during the study and for one day after treatment ends.
Exclusion criteria: The trial excludes patients with certain pre-existing conditions or those who do not meet the specific diagnostic criteria for acquired hemophagocytic syndrome.
Study focus: The primary goal is to measure survival with a decrease in the SOFA score by at least 3 points by day 7. Secondary endpoints include overall survival, changes in temperature, and various biological markers related to hemophagocytic syndrome such as ferritin levels and white blood cell count. The study also monitors the safety of ruxolitinib throughout the treatment period, which lasts up to 28 days.
Investigational drug: Ruxolitinib, provided as Jakavi 5 mg tablets, is taken orally and works by inhibiting enzymes known as Janus kinases that play a role in inflammation and immune system activation.
Study on Etoposide for Patients with Severe Hemophagocytic Lymphohistiocytosis in Intensive Care
This study compares two different strategies for starting treatment with etoposide in patients with severe HLH who require intensive care. One strategy involves starting the treatment early, within 12 hours of inclusion in the study, while the other involves delaying the start until 48 hours later, but only if the patient’s condition does not improve.
Inclusion criteria: Adult patients with a confirmed diagnosis of HLH must meet 5 or more specific criteria including fever, enlarged spleen, low blood cell counts affecting 2 or 3 types of blood cells, high levels of fats in the blood or low levels of blood clotting proteins, and presence of certain cells eating other blood cells. This must be the patient’s first episode of HLH. Patients must be admitted to an intensive care unit and have one or more organ failures, which may include circulatory failure, respiratory failure requiring significant oxygen support or mechanical ventilation, kidney failure, or reduced consciousness with a Glasgow Coma Scale score of 13 or less.
Exclusion criteria: Patients who do not have HLH or who fall outside the specified age range cannot participate.
Study focus: The study monitors patients’ condition using the modified Sequential Organ Failure Assessment score to evaluate organ failures. Researchers will track various outcomes including time to death, number of ventilator-free days, length of stay in the intensive care unit, and other health indicators such as normalization of fibrinogen, decrease in ferritin, and decrease in triglycerides.
Investigational drug: Etoposide is administered intravenously and works by inhibiting an enzyme called topoisomerase II, which is essential for DNA replication and cell division. It is part of the chemotherapy drug class.
Study of emapalumab in children and adults with Macrophage Activation Syndrome (MAS) occurring in Still’s Disease or Systemic Lupus Erythematosus
This study tests emapalumab in patients with Macrophage Activation Syndrome that occurs as a complication of Still’s Disease or Systemic Lupus Erythematosus. MAS is a severe inflammatory condition where the immune system becomes overactive, causing inflammation throughout the body.
Inclusion criteria: Patients between 6 months and 80 years of age with confirmed active MAS characterized by fever and specific blood test results may be eligible. They must have already received high-dose intravenous steroids for at least 3 days without adequate improvement. For the first group of patients, a confirmed diagnosis of systemic juvenile idiopathic arthritis or Adult onset Still’s disease is required. For the second group, confirmed systemic lupus erythematosus is necessary. Women who can become pregnant must use effective birth control methods during treatment and for 6 months after the last dose.
Exclusion criteria: Patients with active or chronic infections including tuberculosis, HIV, or hepatitis B or C cannot participate. Other exclusions include previous treatment with cell or gene therapy within 6 months, history of cancer within the past 5 years, severe heart conditions, severe liver or kidney problems, current pregnancy or breastfeeding, known allergic reactions to similar medications, recent participation in other clinical trials, mental conditions that could interfere with following study procedures, and recent use of live vaccines.
Study focus: The study will evaluate whether emapalumab can effectively treat MAS in patients who have not responded well enough to standard high-dose steroids. Participants will receive emapalumab through intravenous infusion for up to 28 days, with a maximum daily dose of 6 milligrams per kilogram of body weight. Patients will be monitored for 8 weeks after starting treatment to evaluate how well the medication works and whether it allows patients to reduce their steroid medication use.
Investigational drug: Emapalumab is a monoclonal antibody that works by targeting and blocking interferon-gamma, a protein that plays a key role in inflammation. This helps control the overactive immune system response and reduce inflammation in the body.
Study on Itacitinib for Treating Non-Severe Hemophagocytic Lymphohistiocytosis in Adults
This clinical trial focuses on adults with non-severe haemophagocytic lymphohistiocytosis and tests whether itacitinib, taken in tablet form, can help improve symptoms by reducing the excessive immune response.
Inclusion criteria: Patients must be 18 years or older with non-severe HLH that is either new or has returned. Patients should not have other diseases requiring specific treatment and should not have severe symptoms or organ failure. To qualify, patients must show major criteria such as fever, enlarged spleen, and cytological features of hemophagocytosis. They must also show minor criteria including swollen lymph nodes, low blood cell counts affecting more than two types of blood cells, high levels of fats in the blood or low levels of blood clotting proteins, and elevated ferritin levels. An HScore of 169 or higher is required. Women of childbearing potential must have a negative pregnancy test and use reliable contraception during the study.
Exclusion criteria: Patients with severe forms of HLH cannot participate. The study is limited to adults only, excluding anyone under 18 years of age.
Study focus: The study will evaluate how many participants experience a complete or partial improvement in their condition after 15 days of treatment with itacitinib. Throughout the study, participants will receive regular check-ups to assess their health and the impact of the treatment.
Investigational drug: Itacitinib is administered orally in tablet form and works by inhibiting the Janus kinase pathway, which plays a crucial role in the signaling processes of immune cells. It is classified as a JAK inhibitor, helping to regulate the immune system’s activity.
Summary
The current landscape of clinical trials for haemophagocytic lymphohistiocytosis shows a concentration of research activity in France, with 4 out of 5 trials taking place there. This reflects the country’s significant involvement in advancing treatment options for this rare and serious condition.
A notable trend is the focus on JAK inhibitors, with three trials testing different medications from this drug class: ruxolitinib in two separate studies targeting different patient populations, and itacitinib in another. This suggests growing interest in the potential of JAK inhibitors to control the excessive immune activation characteristic of the condition.
The trials address different severity levels and patient populations, ranging from infants to older adults. Some studies focus on first-line treatments for children, while others target critically ill adults in intensive care or patients with non-severe forms of the disease. One trial specifically addresses Macrophage Activation Syndrome occurring as a complication of other autoimmune conditions.
The variety of approaches being tested, including traditional chemotherapy agents like etoposide, monoclonal antibodies like emapalumab, and newer targeted therapies like JAK inhibitors, demonstrates the ongoing effort to find more effective and better-tolerated treatment options for this challenging condition.
