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Hemophagocytic Lymphohistiocytosis (HLH)Phase 2/3NCT07626398

All-Trans Retinoic Acid for the Treatment of Hemophagocytic Lymphohistiocytosis

A Phase 2/3 study testing ATRA in people with Hemophagocytic Lymphohistiocytosis (HLH), run by Beijing Anzhen Hospital.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Hemophagocytic Lymphohistiocytosis (HLH)
What is being tested?
ATRA
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
No sites listed yet
Study dates
1 Jun 2026to 1 Jun 2029
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

About this study

Official title: An Open-Label Study Evaluating the Safety and Efficacy of All-Trans Retinoic Acid in Patients With Hemophagocytic Lymphohistiocytosis

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.

Being tested
ATRA
Medical subject headings
Lymphohistiocytosis, Hemophagocytic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ATRADrug

    All-trans retinoic acid (ATRA) will be administered orally as frontline treatment for patients with active hemophagocytic lymphohistiocytosis (HLH). ATRA will be given at a dose of 45 mg/m²/day in two divided doses, according to the study protocol. Dose rounding, dose reduction, temporary interruption, or discontinuation will be allowed based on toxicity, organ function, and investigator assessment. Standard supportive care, anti-infective treatment, transfusion support, organ function support, and treatment of underlying triggers or diseases are permitted. Additional HLH-directed therapy or rescue treatment may be introduced at the investigator's discretion for patients with inadequate response, disease progression, or life-threatening clinical deterioration.

Study groups in NCT07626398
Study groupRoleWhat they receive
TreatmentExperimentalNot described
Receives: Drug: ATRA

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. ATRA Efficacy for HLH

    Overall response rate will be assessed at Week 4 and week 8 after initiation of ATRA treatment. Overall response is defined as achievement of complete response, partial response, or HLH improvement. Complete response is defined as normalization of HLH-related clinical and laboratory abnormalities, including resolution of fever and splenomegaly, recovery of cytopenias, improvement of coagulation abnormalities, reduction of hyperferritinemia, absence of active central nervous system manifestations, and no sustained worsening of soluble CD25 levels. Partial response is defined as normalization of at least three HLH-related abnormalities. HLH improvement is defined as at least 50% improvement from baseline in at least three HLH-related abnormalities. HLH-related abnormalities to be assessed include fever, splenomegaly, central nervous system symptoms when present, complete blood count, fibrinogen and/or D-dimer, serum ferritin, and soluble CD25.

    Measured: From enrollment to the end of treatment at 8 weeks

  2. Adverse effects of ATRA

    Safety will be assessed by the incidence, severity, seriousness, and relationship to study treatment of treatment-emergent adverse events. An adverse event is defined as any unfavorable and unintended sign, symptom, disease, or abnormal laboratory finding that occurs after initiation of ATRA treatment, whether or not considered related to ATRA.

    Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events. Serious adverse events, grade 3 or higher adverse events, adverse events leading to dose interruption, dose reduction, treatment discontinuation, rescue HLH-directed therapy, hospitalization, or death will be recorded and summarized.

    Measured: From enrollment to the end of treatment at 8 weeks

Secondary outcomes (1)

  1. Survival of HLH patients

    Overall survival will be assessed from the date of initiation of ATRA treatment to the date of death from any cause. Patients who are alive at the time of analysis will be censored at the date of last follow-up. Survival status will be recorded during the study treatment period and follow-up period.

    Measured: From initiation of ATRA treatment up to 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Jun 2026
  2. Study start1 Jun 2026 (estimated)
  3. Primary completion1 Jun 2028 (estimated)
  4. Study completion1 Jun 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07626398
Sponsor's protocol ID
ATRA-HLH
Status last verified
Jun 2026
First submitted
27 May 2026
Last updated
4 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing ATRA in people with Hemophagocytic Lymphohistiocytosis (HLH), run by Beijing Anzhen Hospital.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ATRA Efficacy for HLH (time frame: From enrollment to the end of treatment at 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07626398.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.

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