ClinicalTrials.gov record NCT07626398
All-Trans Retinoic Acid for the Treatment of Hemophagocytic Lymphohistiocytosis
An Open-Label Study Evaluating the Safety and Efficacy of All-Trans Retinoic Acid in Patients With Hemophagocytic Lymphohistiocytosis
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This open‑label study gives all participants oral all‑trans retinoic acid (ATRA) as initial therapy for active hemophagocytic lymphohistiocytosis (HLH). It enrolls adults with newly diagnosed or treatment‑naïve active HLH and follows them for response and safety during the first 8 weeks, with survival tracked up to 6 months. The study is a single‑group Phase 2/3 trial that measures clinical response, inflammatory markers, organ function, and adverse events.
What it is studying. The study tests ATRA as a first‑line treatment for active HLH and measures whether patients show clinical response, changes in HLH‑related inflammatory markers and organ function, and what adverse events occur.
What the researchers hope to learn. To evaluate the safety and preliminary efficacy of ATRA when used as initial therapy for active HLH. To measure overall response rates, changes in HLH‑related laboratory and clinical markers, treatment‑related adverse events, and short‑term survival to inform further clinical development.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- ATRA
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
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.
- 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.
- Ability to understand and willingness to sign written informed consent. For patients unable to provide consent because of disease severity, consent may be provided by a legally authorized representative according to local regulations.
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.
- Uncontrolled hypertriglyceridemia or other metabolic abnormality that, in the investigator's judgment, would make ATRA treatment unsafe.
- Concomitant use of vitamin A supplements, other systemic retinoids, or medications with unacceptable interaction risk that cannot be discontinued.
- Any other condition that, in the investigator's judgment, would interfere with patient safety, protocol compliance, or interpretation of study results.
Study description and what participation involves
The registry record has no detailed description beyond the summary above.
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Participants will take oral all‑trans retinoic acid (ATRA) per the study dosing schedule, with allowed dose adjustments, interruptions, or discontinuation for toxicity. They will have regular clinic visits for physical exams, blood tests and other assessments of HLH signs, inflammatory markers, organ function, and safety monitoring during an initial treatment period (assessments reported through 8 weeks) and follow‑up for survival up to 6 months. Standard supportive care and treatments for underlying triggers are permitted; additional HLH‑directed or rescue therapies may be started by the investigator if the patient does not respond or worsens. Participants of childbearing potential must follow the study contraception requirements.
How the study is structured. All participants receive oral ATRA (single experimental group, open‑label). Response and safety are assessed at Week 4 and Week 8; overall survival is tracked up to 6 months. Dose adjustments or additional HLH‑directed therapy are allowed per investigator judgment.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The registry says recruitment has not started. When is it expected to open, and can I register interest now?
- No sites are listed on the registry yet. Where will the study take place?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on hemophagocytic lymphohistiocytosis
Important dates
- Study start
- Jun 1, 2026 (estimated)
- Primary completion
- Jun 1, 2028 (estimated)
- Study completion
- Jun 1, 2029 (estimated)
- Target enrollment
- 30 participants (estimated)
- Last updated on registry
- Jun 4, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Beijing Anzhen Hospital
- Principal investigator
- Yini Wang, Doctor
Beijing Anzhen Hospital
Participating sites
Study locations have not been posted on ClinicalTrials.gov yet. This study is not yet recruiting, so sites may be added when recruitment begins.
Terms used on this page · explanations by MedicalUpdates.ai
- immunosuppressive
- A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
- treatment-naïve
- Has not previously received the treatment, or the type of treatment, that the study is about.
- adverse events
- Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome.
- performance status
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- written informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- legally authorized representative
- A person who is legally allowed to make decisions, including consent to research, on behalf of someone who cannot consent for themselves.
- investigational
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- corticosteroids
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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