All-Trans Retinoic Acid for the Treatment of Hemophagocytic Lymphohistiocytosis (NCT07626398) | Clinical Trial Compass
Not Yet RecruitingPhase 2/3
All-Trans Retinoic Acid for the Treatment of Hemophagocytic Lymphohistiocytosis
30 participantsStarted 2026-06-01
Plain-language summary
This study is designed to evaluate the safety and preliminary efficacy of all-trans retinoic acid (ATRA) as an initial treatment for patients with active hemophagocytic lymphohistiocytosis (HLH). HLH is a severe hyperinflammatory syndrome caused by excessive activation of immune cells and uncontrolled cytokine release. Current treatment often requires intensive immunosuppressive or cytotoxic therapy, which may be associated with significant toxicity.
ATRA is an orally available agent that has been widely used in other hematologic diseases and has immunomodulatory effects. Preclinical studies suggest that ATRA may help control HLH-related inflammation and improve immune dysregulation. In this study, patients with newly diagnosed or treatment-naïve active HLH will receive ATRA-based initial therapy. The study will assess clinical response, changes in HLH-related inflammatory markers, organ function, viral or disease-related parameters when applicable, and treatment-related adverse events.
The goal of this study is to determine whether ATRA can provide a safe and feasible initial therapeutic approach for active HLH and support further clinical development of ATRA-based treatment strategies in this disease.
Who can participate
Age range
18 Years – 65 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Age ≥18 years.
. Patients diagnosed with active hemophagocytic lymphohistiocytosis according to HLH-2004 diagnostic criteria or the investigator's clinical assessment.
. Newly diagnosed or treatment-naïve active HLH requiring initial HLH-directed therapy.
. Presence of active disease manifestations, including at least one of the following: persistent fever, cytopenia, hyperferritinemia, splenomegaly, hypofibrinogenemia and/or hypertriglyceridemia, elevated soluble CD25, hemophagocytosis, reduced or absent NK-cell activity, or other HLH-related organ involvement.
. Eastern Cooperative Oncology Group performance status of 0-3, or performance status considered acceptable by the investigator in the context of active HLH.
. Adequate ability to receive oral medication, or ability to receive ATRA through an appropriate enteral route.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
ATRA Efficacy for HLH
Timeframe: From enrollment to the end of treatment at 8 weeks
2
Adverse effects of ATRA
Timeframe: From enrollment to the end of treatment at 8 weeks
. Expected survival of more than 48 hours in the judgment of the investigator.
. Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use effective contraception during treatment and for an appropriate period after the last dose of ATRA.
Exclusion criteria
. Prior systemic HLH-directed therapy for the current HLH episode, including etoposide-based therapy, ruxolitinib, emapalumab, alemtuzumab, PD-1 blockade, or other investigational HLH-directed treatment. Short-term corticosteroids, supportive care, anti-infective therapy, or emergency treatment before enrollment may be allowed at the investigator's discretion.
. Known hypersensitivity to all-trans retinoic acid, tretinoin, retinoids, or any component of the study drug.
. Pregnant or breastfeeding women.
. Patients with acute promyelocytic leukemia or other diseases for which ATRA is being used as standard leukemia-directed therapy.
. Severe uncontrolled infection, shock, respiratory failure, bleeding, or organ failure that, in the investigator's judgment, would make participation unsafe or prevent assessment of study treatment.
. Severe hepatic dysfunction not primarily attributed to HLH, such as total bilirubin or transaminase levels considered unsafe for ATRA administration by the investigator.
. Severe renal dysfunction requiring dialysis before enrollment, unless considered related to HLH and acceptable by the investigator.
. Active intracranial hypertension, pseudotumor cerebri, or uncontrolled severe neurologic disease that may increase the risk of ATRA-related toxicity.