A Phase 2/3 interventional study of ATRA in Hemophagocytic Lymphohistiocytosis (HLH), sponsored by Beijing Anzhen Hospital. Not yet recruiting. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-06-04.
Sponsored by Beijing Anzhen Hospital · Phase 2/3, Interventional, and Treatment
Help build ClinicalTrials.gg — short surveys, remote interviews or testing, in your language. Take part →
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.
111 studies on the registry are indexed under Lymphohistiocytosis, Hemophagocytic; 41 are open to participants now.
This study's planned enrollment of 30 is close to the median of 30 across 75 interventional studies indexed under Lymphohistiocytosis, Hemophagocytic.
Browse Lymphohistiocytosis, Hemophagocytic studies →Beijing Anzhen Hospital is the lead sponsor of 193 studies on the registry; 103 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Age ≥18 years.
Prior systemic HLH-directed therapy for the current HLH episode, including etoposide-based therapy, ruxolitinib, emapalumab, alemtuzumab, blockade, or other HLH-directed treatment. Short-term , supportive care, anti-infective therapy, or emergency treatment before enrollment may be allowed at the investigator's discretion.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: ATRA
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.
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.
Time frame: From enrollment to the end of treatment at 8 weeks
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.
Time frame: From enrollment to the end of treatment at 8 weeks
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.
Time frame: From initiation of ATRA treatment up to 6 months
No study locations are listed for this record.
Plan to share: Yes
No publications or documents are linked to this record.
Start is estimated for Jun 2026; primary completion for Jun 2028, 24 months later.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Tretinoin
Lymphohistiocytosis, Hemophagocytic →