Langerhans Cell HistiocytosisPhase 2LUCASNCT07728201
Response-adapted Luvometinib With or Without Cytarabine in Langerhans Cell Histiocytosis
A Phase 2 study testing Luvometinib and Luvometinib, Cytarabine. in people with Langerhans Cell Histiocytosis, run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Langerhans Cell Histiocytosis
- What is being tested?
- Luvometinib and Luvometinib, Cytarabine.
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 30 Jun 2026to 30 Jun 2030
- Phase
- Phase 2
- 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 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Histologically confirmed Langerhans cell histiocytosis (LCH).
- Age 10 years or older.
- Systemic treatment indication and at least one PET response criteria-evaluable lesion.
- Expected survival of at least 12 weeks, as judged by the investigator, and able to undergo protocol-specified treatment, assessments, and follow-up.
- ECOG performance status 0-2 or Lansky score >=60.
- Adequate organ function as defined in the protocol.
- Written informed consent from adult participants or legal guardians, with participant assent when applicable.
Who cannot join
- Hypersensitivity to luvometinib or any excipient.
- Concurrent other malignant tumor.
- Pregnancy or breastfeeding.
- Failure to meet protocol contraception requirements.
- Active bacterial, fungal, or viral infection.
- Significant retinal disease or glaucoma.
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- NYHA class >=3 heart failure or LVEF <50%.
- Psychiatric disease or other condition preventing protocol compliance.
- Investigator judgment that participation is unsuitable.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai
Qi Zhu, 0086-18116215629, zhuqi70@hotmail.com
About this study
Official title: Luvometinib Monotherapy or Combined With Cytarabine for Langerhans Cell Histiocytosis: A Response-adapted, Interventional, Prospective Study
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.
- Conditions
- Langerhans Cell Histiocytosis
- Being tested
- Luvometinib, Luvometinib, Cytarabine.
- Keywords
- Langerhans cell histiocytosis, LCH, luvometinib, cytarabine, MEK inhibitor, response-adapted therapy, PET/CT, cfDNA, ctDNA, MAPK pathway, LUCAS
- Medical subject headings
- Histiocytosis, Langerhans-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LuvometinibDrug
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, Cytarabine.Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| A: CMR response path | Experimental | 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. Receives: Drug: Luvometinib |
| B: Non-CMR response path | Experimental | 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. Receives: Drug: Luvometinib, Cytarabine. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
Secondary outcomes (6)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: At the end of Cycle 12, 18, and 24 (each cycle is 35 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2026
- Study start30 Jun 2026 (estimated)
- Primary completion31 Jul 2028 (estimated)
- Study completion30 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Langerhans Cell HistiocytosisStudies of the same condition, open and under way.
- More trials run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- All participants receive luvometinib induction for six 35-day cycles. At cycle 6 PET/CT, participants with complete metabolic response enter the A response path and continue luvometinib maintenance for 18 additional cycles. Participants without complete metabolic response who are suitable to continue protocol treatment enter the B response path and receive luvometinib plus cytarabine for 12 cycles followed by luvometinib maintenance for 6 cycles. Participants with confirmed progression or unsuitable status may receive combination treatment when appropriate, other standard therapy, or discontinue study treatment. Progression is counted for PFS and, after CMR/PMR, for DOR. Survival, subsequent anti-LCH therapy, SAEs, study-related AEs, and clinically performed disease assessments may be followed unless follow-up consent is withdrawn.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Qi Zhu, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07728201
- Sponsor's protocol ID
- LUCAS-2026-V4.0
- Acronym
- LUCAS
- Status last verified
- Jul 2026
- First submitted
- 13 Jul 2026
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 27 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Luvometinib Monotherapy or Combined With Cytarabine for Langerhans Cell Histiocytosis: A Response-adapted, Interventional, Prospective Study
- ClinicalTrials.gov ID
- NCT07728201
- Acronym / sponsor ID
- LUCAS / LUCAS-2026-V4.0
- Conditions
- Langerhans Cell Histiocytosis
- Keywords
- Langerhans cell histiocytosis, LCH, luvometinib, cytarabine, MEK inhibitor, response-adapted therapy, PET/CT, cfDNA
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong UniversityUniversity, hospital or other
- Collaborators
- Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
- Study start
- 30 Jun 2026 (estimated)
- Primary completion
- 31 Jul 2028 (estimated)
- Study completion
- 30 Jun 2030 (estimated)
- First posted
- 27 Jul 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- All participants receive luvometinib induction for six 35-day cycles. At cycle 6 PET/CT, participants with complete metabolic response enter the A response path and continue luvometinib maintenance for 18 additional cycles. Participants without complete metabolic response who are suitable to continue protocol treatment enter the B response path and receive luvometinib plus cytarabine for 12 cycles followed by luvometinib maintenance for 6 cycles. Participants with confirmed progression or unsuitable status may receive combination treatment when appropriate, other standard therapy, or discontinue study treatment. Progression is counted for PFS and, after CMR/PMR, for DOR. Survival, subsequent anti-LCH therapy, SAEs, study-related AEs, and clinically performed disease assessments may be followed unless follow-up consent is withdrawn.
| Arm | Type | Receives |
|---|---|---|
| A: CMR response path | Experimental | Drug: LuvometinibAll 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. |
| B: Non-CMR response path | Experimental | Drug: Luvometinib, Cytarabine.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. |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Histologically confirmed Langerhans cell histiocytosis (LCH).
- Age 10 years or older.
- Systemic treatment indication and at least one PET response criteria-evaluable lesion.
- Expected survival of at least 12 weeks, as judged by the investigator, and able to undergo protocol-specified treatment, assessments, and follow-up.
- ECOG performance status 0-2 or Lansky score >=60.
Key exclusion criteria (9 listed)
- Hypersensitivity to luvometinib or any excipient.
- Concurrent other malignant tumor.
- Pregnancy or breastfeeding.
- Failure to meet protocol contraception requirements.
- Active bacterial, fungal, or viral infection.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LuvometinibLuvometinib 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. | Drug | A: CMR response path |
| Luvometinib, Cytarabine.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. | Drug | B: Non-CMR response path |
Primary outcome
Objective response rate after six cycles of luvometinib induction by blinded independent central review
Time frame: At completion of six 35-day cycles, approximately week 30 / target C7D1 +/- 7 days
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.
Incidence of adverse events and serious adverse events
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
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.
6 secondary outcomes
Kaplan-Meier estimated progression-free survival rate at 24 months
Time frame: 24 months after first dose
Time to response among CMR/PMR responders
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
Time frame: 12 and 24 months after first dose
Objective response rate at cycles 12, 18, and 24
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
Time frame: At the end of Cycle12, 18, and 24 (each cycle is 35 days)
Clinical benefit rate at cycles 12, 18, and 24
Time frame: At the end of Cycle 12, 18, and 24 (each cycle is 35 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jul 2026.
- Individual participant dataSharing planned: 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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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Luvometinib and Luvometinib, Cytarabine. in people with Langerhans Cell Histiocytosis, run by Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University at 1 site in China.
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 7 inclusion and 9 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 27 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 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.
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?
Contact Qi Zhu (0086-18116215629, zhuqi70@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate after six cycles of luvometinib induction by blinded independent central review (time frame: At completion of six 35-day cycles, approximately week 30 / target C7D1 +/- 7 days). 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?
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 27 Jul 2026.