A Phase 2 interventional study of Luvometinib and Luvometinib, Cytarabine. in Langerhans Cell Histiocytosis, sponsored by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University. Not yet recruiting at 1 site in China. Open to participants aged 10 Years and older. Per ClinicalTrials.gov, last updated 2026-07-27.
Sponsored by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University · Phase 2, Interventional, and Treatment
This single-center, prospective, interventional phase 2 study evaluates a response-adapted treatment strategy for patients aged 10 years and older with histologically confirmed Langerhans cell histiocytosis requiring systemic therapy. All participants receive six 35-day cycles of luvometinib induction. Post-induction treatment follows the cycle 6 PET/CT response: participants with complete metabolic response continue luvometinib maintenance without cytarabine, whereas participants without complete metabolic response who are judged suitable to continue protocol treatment receive luvometinib plus cytarabine followed by luvometinib maintenance; participants with progression or otherwise unsuitable to continue protocol treatment may receive other standard therapy or discontinue study treatment per protocol. The primary endpoint is objective response rate after six cycles by blinded independent central review.
81 studies on the registry are indexed under Histiocytosis, Langerhans-Cell; 23 are open to participants now.
This study's planned enrollment of 30 is above the median of 24 across 64 interventional studies indexed under Histiocytosis, Langerhans-Cell.
Browse Histiocytosis, Langerhans-Cell studies →Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University is the lead sponsor of 164 studies on the registry; 73 are open to participants now.
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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.
Exclusion Criteria:
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.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
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.
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.
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.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
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.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
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.
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.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
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.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All participants receive luvometinib induction for six 35-day cycles before response assessment. Participants achieving complete metabolic response after induction continue luvometinib maintenance without cytarabine for 18 additional 35-day cycles unless progression, unacceptable toxicity, death, or withdrawal occurs. If confirmed progression occurs during maintenance, participants may transition to combination treatment, receive other standard salvage therapy, or discontinue study treatment; progression is counted as a PFS event and, if the participant previously achieved CMR or PMR, a DOR event. Follow-up continues unless follow-up consent is withdrawn.
Drug: Luvometinib
All participants receive luvometinib induction for six 35-day cycles before response assessment. Participants not achieving complete metabolic response and judged suitable to continue protocol treatment receive luvometinib plus cytarabine for 12 35-day cycles, followed by luvometinib maintenance for 6 additional 35-day cycles.
Drug: Luvometinib, Cytarabine.
Luvometinib is administered orally once daily in 35-day cycles. Adult participants receive 8 mg once daily. Pediatric participants receive body-surface-area-adjusted dosing at 5 mg/m² once daily, rounded according to protocol with a maximum single dose of 8 mg. Luvometinib is used during induction and maintenance according to the assigned response path.
Luvometinib is administered as described for induction and maintenance. In the B response path, cytarabine is administered at 100 mg/m² by subcutaneous injection on days 1-5 of each 35-day cycle for 12 cycles, followed by luvometinib maintenance for 6 additional 35-day cycles.
Objective response rate after six cycles of luvometinib induction by blinded independent central review
Proportion of full analysis set participants achieving complete metabolic response (CMR) or partial metabolic response (PMR) by PET response criteria at the cycle 6 assessment window (target C7D1 +/- 7 days), as determined by blinded independent central review. No subsequent confirmatory PET/CT is required. The analysis is descriptive and will report the point estimate with an exact two-sided 95% confidence interval; no confirmatory hypothesis test is planned. Mild out-of-window assessments may be included with protocol deviation documentation if no major treatment or disease-status change affects interpretation. Clearly out-of-window, non-evaluable, or unreliable assessments, death, progression, treatment discontinuation due to toxicity, withdrawal from study treatment, or non-evaluable imaging before the cycle 6 assessment are counted as non-responders.
Time frame: At completion of six 35-day cycles, approximately week 30 / target C7D1 +/- 7 days
Incidence of adverse events and serious adverse events
AEs, TRAEs, grade \>=3 AEs, SAEs, deaths, and clinically significant laboratory abnormalities summarized by NCI-CTCAE v5.0 and MedDRA SOC/PT. All AEs after informed consent will be recorded; treatment-emergent summaries will start at first study treatment and be summarized by actual exposure period, including luvometinib monotherapy, luvometinib plus cytarabine, and post-progression or salvage treatment descriptions as applicable. SAEs, study-related AEs, pregnancy, and important safety information after study treatment discontinuation may be followed during continued follow-up unless follow-up consent is withdrawn.
Time frame: Routine AE recording: consent to 30 days after last study treatment; TEAE summaries from first dose; SAEs, study-related AEs, pregnancy, and important safety information followed per protocol
Kaplan-Meier estimated progression-free survival rate at 24 months
Kaplan-Meier estimated proportion of participants without PRC-defined PMD, investigator-confirmed clinical progression supported by clinically performed imaging or documentation after study treatment discontinuation, or death from any cause. Clinically performed data may be used to record PFS progression events but are not included in ORR/DCR/CBR endpoint analyses. Such PFS events may be investigator-adjudicated, with BICR review or audit when feasible; if BICR review is not feasible, the source, assessment date, adjudicator, rationale, and reason will be documented. A sensitivity analysis will include only BICR-confirmed progression, protocol-window imaging-confirmed progression meeting PRC/BICR requirements, or death from any cause.
Time frame: 24 months after first dose
Time to response among CMR/PMR responders
Time from first dose to first documented CMR or PMR. TTR will be calculated only for participants who achieve CMR or PMR. SMD is not considered a response for TTR; if SMD precedes later PMR/CMR, TTR is measured from first dose to first documented PMR/CMR. Participants with SMD only are not assigned a TTR value.
Time frame: From first dose through the first documented CMR/PMR, up to 24 cycles (each cycle is 35 days)
Kaplan-Meier estimated overall survival rate at 12 and 24 months
Kaplan-Meier estimated survival rate from first dose to death from any cause. Participants who transition to combination treatment, receive salvage therapy, or discontinue study treatment remain in survival follow-up unless follow-up consent is withdrawn.
Time frame: 12 and 24 months after first dose
Objective response rate at cycles 12, 18, and 24
Proportion of evaluable participants achieving CMR or PMR by PRC/BICR at the cycle 12, 18, and 24 assessment windows. Later ORR is summarized descriptively using the evaluable response set at each time point; the FAS denominator, number evaluable, and reasons for missing or non-evaluable assessments will also be reported. These later visits evaluate durability and subsequent response patterns and do not confirm the primary ORR endpoint.
Time frame: At the end of Cycle 12, 18, and 24 (each cycle is 35 days)
Disease control rate at cycles 12, 18, and 24
Proportion of evaluable participants achieving CMR, PMR, or stable metabolic disease (SMD) by PRC/BICR at the cycle 12, 18, and 24 assessment windows. DCR is summarized descriptively using the evaluable response set at each time point; the FAS denominator, number evaluable, and missing or non-evaluable reasons will be listed.
Time frame: At the end of Cycle12, 18, and 24 (each cycle is 35 days)
Clinical benefit rate at cycles 12, 18, and 24
Proportion of evaluable participants who achieve CMR, PMR, or SMD and maintain disease control for at least 24 weeks. The 24-week duration is counted from the first assessment date documenting CMR, PMR, or SMD to first PMD, death, or loss of disease control, whichever occurs first. Node-specific CBR at cycles 12, 18, and 24 will count only participants who have met the at-least-24-week disease control duration requirement by that assessment node. Participants pending confirmation or not yet meeting the duration requirement remain in the denominator and will be listed separately.
Time frame: At the end of Cycle 12, 18, and 24 (each cycle is 35 days)
Duration of response among CMR/PMR responders
Duration of response will be analyzed among responders only, defined as participants who achieve CMR or PMR. DOR is measured from the first documented CMR/PMR to first documented PMD or death from any cause; responders without progression or death will be censored at the date of last evaluable disease assessment. SMD is not considered a response for DOR; if SMD precedes later PMR/CMR, DOR starts at the first documented PMR/CMR. Participants with SMD only are not included in the DOR analysis.
Time frame: From first documented CMR/PMR through progression, death, or last evaluable disease assessment, up to 24 cycles (each cycle is 35 days)
Spearman Correlation Between Changes in MAPK VAF in cfDNA and peripheral blood cell DNA
Change from baseline in the proportion of MAPK pathway variant allele fraction (VAF) in plasma cell-free DNA (cfDNA) and peripheral blood cell DNA, including tumor-derived cfDNA (ctDNA) when detectable, with Spearman's rank correlation coefficient calculated between these proportional changes. These biomarkers will not independently determine treatment assignment or response assessment. After study treatment discontinuation, additional research cfDNA testing is not mandatory; clinically performed or voluntarily completed relevant testing may be recorded descriptively and will not be included in protocol-defined efficacy endpoint analyses unless it occurs within a protocol-defined window and meets applicable protocol requirements.
Time frame: Baseline and the end of cycles 6, 12, 18, and 24 as applicable (each cycle is 35 days)
Spearman Correlation Coefficient for Changes in MAPK VAF in cfDNA/Peripheral Blood Cell DNA and SUVmax change
Spearman's rank correlation coefficient between change from baseline in MAPK pathway VAF in plasma cfDNA/peripheral blood cell DNA and change from baseline in SUVmax of target lesions. Exploratory only, not for treatment assignment or response assessment.
Time frame: Baseline and cycles 6, 12, 18, and 24 as applicable (each cycle is 35 days)
Quality-of-life scores (adults)
EORTC QLQ-C30 for adults
Time frame: Baseline and the end of Cycle 6, 12, 18, and 24 as applicable (each cycle is 35 days)
Quality-of-life scores (participants aged 10-17)
PedsQL 4.0 for participants aged 10-17.
Time frame: Baseline and the end of Cycle 6, 12, 18, and 24 as applicable (each cycle is 35 days)
Plan to share: No — No individual participant-level data sharing is currently planned. Aggregated results will be reported. Any future participant-level data disclosure required by regulators, journals, or institutional policy would require separate ethics and institutional approval, data-use agreements, and applicable human genetic resources and personal information compliance.
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Studies of the drug tested here: Luvometinib
Histiocytosis, Langerhans-Cell →
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University →