Cutaneous Lupus Erythematosus (CLE)Phase 3LEISURENCT06965244
Lenalidomide vs Methotrexate in Difficult-to-treat Cutaneous Lupus Erythematosus
A Phase 3 study testing Lenalidomide and Methotrexate (MTX) in people with Cutaneous Lupus Erythematosus (CLE), run by Assistance Publique - Hôpitaux de Paris.
Trial summary
Cutaneous lupus erythematosus (CLE) is a heterogeneous inflammatory autoimmune disease associated or not with systemic lupus erythematosus (SLE). Active CLE often cause pain/burning sensation and may lead to permanent visible scars and cicatricial alopecia, with psycho-social consequences/poor quality of life. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cutaneous Lupus Erythematosus (CLE)
- What is being tested?
- Lenalidomide and Methotrexate (MTX)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 122 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2025to 1 Apr 2029
- Phase
- Phase 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients of at least 18 years of age
- Affiliated to the French social security
- Able to provide written informed consent
- Histologically-confirmed diagnosis of active CLE with or without associated SLE, either historical or at screening
- CLASI-A score ≥ 8 at both screening and randomization
- Active CLE despite
Show all 10Show fewer
- AMs agents used for at least 3 months and at stable dose for at least 30 days prior to randomization or previously documented discontinuation of AMs due to poor tolerability an/or side effect and/or
- stable dose of GCs ≤15mg/day and/or
- stable dose of topical corticosteroids (TCS) or topical tacrolimus for at least 30 days prior to randomization
- Accepting monthly plasma pregnancy test and using adequate contraception for at least 4 weeks before and until 4 weeks following treatment
Who cannot join
- Kidney function, liver function, cell blood count and infectious serology incompatible with receiving the study treatments, according to the SMPC of each drug.
- Alcoholism (1/ no more than 10 standard drinks per week, 2/ no more than two standard drinks per day, and 3/ at least two alcohol-free days every week)
- Ongoing cancer, including solid tumors and hematologic malignancies
- Active severe SLE features including lupus nephritis, neuropsychiatric SLE, serositis, severe haematological features (autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura) requiring high dose oral or IV GC and/or mycophenolate mofetil or cyclophosphamide
- Medications:
- Previous failure of methotrexate and lenalidomide prescribed for active CLE
Show all 12Show fewer
- Use of classical immunosuppressant drugs (mycophenolate mofetil, azathioprine), thalidomide, dapsone, retinoids, Janus Kinase inhibitors for CLE or SLE 4 weeks before screening
- Use of biological therapy for CLE or SLE (including belimumab, rituximab, obinituzumab, ustekinumab, anifrolumab) 12 weeks before screening
- Contraindication to use low-dose aspirin: salicylate hypersensitivity, salicylate-induced asthma, constitutional or acquired bleeding disorder, active gastroduodenal ulcer, or history of digestive bleeding.
- Arterial or unprovoked venous thromboembolic events ≤ 5 years (for note antiphospholipid syndrome treated with vitamin K antagonist without thromboembolic events in the last 5 years or patients with positive antiphospholipid autoantibodies will NOT be excluded)
- Pregnant women, breastfeeding or planning to become pregnant during the study treatment period and 1 month after the last dose of study treatment
- Patients under legal protection and inability to comply with study requirement
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Lenalidomide vs mEthotrexate in dIfficult-to-treat cutaneouS lUpus eRythEmatosus : An Assessor-blinded Randomized Clinical Trial
Cutaneous lupus erythematosus (CLE) is a heterogeneous inflammatory autoimmune disease associated or not with systemic lupus erythematosus (SLE). Active CLE often cause pain/burning sensation and may lead to permanent visible scars and cicatricial alopecia, with psycho-social consequences/poor quality of life. First-line antimalarials (AMs) are recommended in CLE in addition to topical corticosteroids/tacrolimus with long-term response rate around 50%. Oral glucocorticosteroids (GCs) are recommended in addition to AMs for short term therapy in severe or widespread active CLE lesions. In non-responders to AMs and low-dose oral GCs, i.e., difficult-to-treat CLE, guidelines recommend the add-on of methotrexate as preferential second-line agent, with an overall efficacy of 50% in observational studies. Thalidomide has shown response rate of ≈90% in CLE in a meta-analysis of observational studies and is recommended as a second or third-line agent. However, potential severe adverse events (AEs) including teratogenicity, peripheral neuropathy and thromboembolic events limit its use.
Biological therapies including belimumab and anifrolumab, are approved only for patients with associated SLE (and not for those with isolated CLE). Their efficacy has been demonstrated as add-on therapy versus placebo but not versus a comparative drug. Moreover, efficacy of belimumab seems limited in difficult to-treat CLE and has not been assessed using validated tool, as the Cutaneous Lupus Erythematosus Disease Area and Severity (CLASI) Index. Anifrolumab seems interesting in CLE associated with SLE, but its use is limited by monthly intravenous infusions, high cost and unknown long-term AEs. Moreover, its efficacy in isolated CLE has not been assessed.
Read more
Lenalidomide is a thalidomide analogue with in vitro 1000 more potent immunomodulatory properties. It is recommended as a third-line treatment in France. With more than 60 treated patients, it showed excellent and rapid efficacy with an absence of drowsiness and peripheral neuropathy with a low-dose regimen of 5 mg/day. The use of lenalidomide was to date limited by its very high cost and its indications were restricted to haematological disorders. For note, the prevention of the higher risk of thromboembolism with lenalidomide requires the daily use of low-dose aspirin.
In France, a generic of lenalidomide is now available with a monthly cost of 2 euros, allowing a broad-scale assessment of its efficacy. Finally, lenalidomide might have a better efficacy than methotrexate.
We hypothesize that lenalidomide would be more efficacious than methotrexate in difficult-to-treat CLE patients with or without associated SLE. We assume that such trial would not be supported by pharmaceutical companies.
- Conditions
- Cutaneous Lupus Erythematosus (CLE)
- Being tested
- Lenalidomide, Methotrexate (MTX)
- Keywords
- systemic lupus erythematosus, cutaneous lupus erythematosus, chronic CLE, lenalidomide, methotrexate, Resistance to anti-malarial
- Medical subject headings
- Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Systemic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LenalidomideDrug
Lenalidomide with oral dose of 5 mg/day during 16 weeks associated with low-dose aspirin of 100 mg/day except for patients already receiving anticoagulant therapy
Methotrexate (MTX)Drug
Methotrexate oral dose of 15 mg per week for individuals < 80 kg, and a dose of 20mg per week for those over 80 kg, along with an equal dose of folic acid supplementation given 48 hours after each dose
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide with aspirin | Experimental | Lenalidomide with low-dose aspirin Receives: Drug: Lenalidomide |
| Methotrexate with folic acid | Active comparator | Methotrexate with low dose of folic acid Receives: Drug: Methotrexate (MTX) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients who achieve decrease of at least 50% from baseline in the CLASI activity (CLASI-A) score
CLASI : Cutaneous LE disease Area and Severity Index
Measured: At week 16
Secondary outcomes (12)
Percentage of patients reaching CLASI-A 70
CLASI : Cutaneous LE disease Area and Severity Index
Measured: At week 16
Proportion of participants who achieve complete or almost complete response (CLASI-A 0-3)
CLASI : Cutaneous LE disease Area and Severity Index
Measured: At week 16
Percentage of patients reaching CLASI-A 70
CLASI : Cutaneous LE disease Area and Severity Index
Measured: At week 24
Proportion of participants who achieve complete or almost complete response (CLASI-A 0-3)
CLASI : Cutaneous LE disease Area and Severity Index
Measured: At week 24
Variation of Quality of life using DLQI
DLQI : Dermatology Life Quality Index
Measured: At week 16
Variation of Quality of life using DLQI
DLQI : Dermatology Life Quality Index
Measured: At week 24
SLE activity using SLEDAI
SLEDAI : Systemic Lupus Erythematosus Disease Activity Index
Measured: Up to 24 weeks
SLE flare using SENELA-SLEDAI Flare Index (SFI)
SELENA : Safety of Estrogens in Lupus Erythematosus National Assessment SLEDAI : Systemic Lupus Erythematosus Disease Activity Index
Measured: Up to 24 weeks
Variation of GCs dose
Measured: Between inclusion and week 24.
Variation of damage in each group using CLASI-D
CLASI : Cutaneous LE disease Area and Severity Index
Measured: At week 24
Variation of damage in each group using CLASI-D
CLASI : Cutaneous LE disease Area and Severity Index
Measured: At week 16
Rate of adverse events
Measured: Up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2025
- Study start1 Oct 2025 (estimated)
- Primary completion1 Feb 2029 (estimated)
- Study completion1 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cutaneous Lupus Erythematosus (CLE)Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The trial is a prospective, multicentre, randomised (1:1), open label, parallel group comparison with blinded assessment of the primary endpoint (PROBE design) conducted for comparing the efficacy and safety of lenalidomide 5 mg/day versus oral methotrexate 15 to 20 mg/week 16 for improving active CLE lesions for patients with isolated CLE or CLE.
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 122 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06965244
- Sponsor's protocol ID
- APHP240920
- Other IDs
- 2024-520089-70-00
- Acronym
- LEISURE
- Status last verified
- May 2025
- First submitted
- 10 Feb 2025
- Last updated
- 11 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Lenalidomide vs mEthotrexate in dIfficult-to-treat cutaneouS lUpus eRythEmatosus : An Assessor-blinded Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT06965244
- Acronym / sponsor ID
- LEISURE / APHP240920
- Conditions
- Cutaneous Lupus Erythematosus (CLE)
- Keywords
- systemic lupus erythematosus, cutaneous lupus erythematosus, chronic CLE, lenalidomide, methotrexate, Resistance to anti-malarial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 122 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 1 Oct 2025 (estimated)
- Primary completion
- 1 Feb 2029 (estimated)
- Study completion
- 1 Apr 2029 (estimated)
- First posted
- 11 May 2025 (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.
Cutaneous lupus erythematosus (CLE) is a heterogeneous inflammatory autoimmune disease associated or not with systemic lupus erythematosus (SLE). Active CLE often cause pain/burning sensation and may lead to permanent visible scars and cicatricial alopecia, with psycho-social consequences/poor quality of life. First-line antimalarials (AMs) are recommended in CLE in addition to topical corticosteroids/tacrolimus with long-term response rate around 50%. Oral glucocorticosteroids (GCs) are recommended in addition to AMs for short term therapy in severe or widespread active CLE lesions. In non-responders to AMs and low-dose oral GCs, i.e., difficult-to-treat CLE, guidelines recommend the add-on of methotrexate as preferential second-line agent, with an overall efficacy of 50% in observational studies. Thalidomide has shown response rate of ≈90% in CLE in a meta-analysis of observational studies and is recommended as a second or third-line agent. However, potential severe adverse events (AEs) including teratogenicity, peripheral neuropathy and thromboembolic events limit its use.
Biological therapies including belimumab and anifrolumab, are approved only for patients with associated SLE (and not for those with isolated CLE). Their efficacy has been demonstrated as add-on therapy versus placebo but not versus a comparative drug. Moreover, efficacy of belimumab seems limited in difficult to-treat CLE and has not been assessed using validated tool, as the Cutaneous Lupus Erythematosus Disease Area and Severity (CLASI) Index. Anifrolumab seems interesting in CLE associated with SLE, but its use is limited by monthly intravenous infusions, high cost and unknown long-term AEs. Moreover, its efficacy in isolated CLE has not been assessed.
Lenalidomide is a thalidomide analogue with in vitro 1000 more potent immunomodulatory properties. It is recommended as a third-line treatment in France. With more than 60 treated patients, it showed excellent and rapid efficacy with an absence of drowsiness and peripheral neuropathy with a low-dose regimen of 5 mg/day. The use of lenalidomide was to date limited by its very high cost and its indications were restricted to haematological disorders. For note, the prevention of the higher risk of thromboembolism with lenalidomide requires the daily use of low-dose aspirin.
In France, a generic of lenalidomide is now available with a monthly cost of 2 euros, allowing a broad-scale assessment of its efficacy. Finally, lenalidomide might have a better efficacy than methotrexate.
We hypothesize that lenalidomide would be more efficacious than methotrexate in difficult-to-treat CLE patients with or without associated SLE. We assume that such trial would not be supported by pharmaceutical companies.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- The trial is a prospective, multicentre, randomised (1:1), open label, parallel group comparison with blinded assessment of the primary endpoint (PROBE design) conducted for comparing the efficacy and safety of lenalidomide 5 mg/day versus oral methotrexate 15 to 20 mg/week 16 for improving active CLE lesions for patients with isolated CLE or CLE.
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide with aspirin | Experimental | Drug: LenalidomideLenalidomide with low-dose aspirin |
| Methotrexate with folic acid | Active comparator | Drug: Methotrexate (MTX)Methotrexate with low dose of folic acid |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients of at least 18 years of age
- Affiliated to the French social security
- Able to provide written informed consent
- Histologically-confirmed diagnosis of active CLE with or without associated SLE, either historical or at screening
- CLASI-A score ≥ 8 at both screening and randomization
Key exclusion criteria (12 listed)
- Kidney function, liver function, cell blood count and infectious serology incompatible with receiving the study treatments, according to the SMPC of each drug.
- Alcoholism (1/ no more than 10 standard drinks per week, 2/ no more than two standard drinks per day, and 3/ at least two alcohol-free days every week)
- Ongoing cancer, including solid tumors and hematologic malignancies
- Active severe SLE features including lupus nephritis, neuropsychiatric SLE, serositis, severe haematological features (autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura) requiring high dose oral or IV GC and/or mycophenolate mofetil or cyclophosphamide
- Medications:
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 |
|---|---|---|
| LenalidomideLenalidomide with oral dose of 5 mg/day during 16 weeks associated with low-dose aspirin of 100 mg/day except for patients already receiving anticoagulant therapy | Drug | Lenalidomide with aspirin |
| Methotrexate (MTX)Methotrexate oral dose of 15 mg per week for individuals < 80 kg, and a dose of 20mg per week for those over 80 kg, along with an equal dose of folic acid supplementation given 48 hours after each dose | Drug | Methotrexate with folic acid |
Primary outcome
Proportion of patients who achieve decrease of at least 50% from baseline in the CLASI activity (CLASI-A) score
Time frame: At week 16
CLASI : Cutaneous LE disease Area and Severity Index
12 secondary outcomes
Percentage of patients reaching CLASI-A 70
Time frame: At week 16
Proportion of participants who achieve complete or almost complete response (CLASI-A 0-3)
Time frame: At week 16
Percentage of patients reaching CLASI-A 70
Time frame: At week 24
Proportion of participants who achieve complete or almost complete response (CLASI-A 0-3)
Time frame: At week 24
Variation of Quality of life using DLQI
Time frame: At week 16
Variation of Quality of life using DLQI
Time frame: At week 24
SLE activity using SLEDAI
Time frame: Up to 24 weeks
SLE flare using SENELA-SLEDAI Flare Index (SFI)
Time frame: Up to 24 weeks
Variation of GCs dose
Time frame: Between inclusion and week 24.
Variation of damage in each group using CLASI-D
Time frame: At week 24
Variation of damage in each group using CLASI-D
Time frame: At week 16
Rate of adverse events
Time frame: Up to 24 weeks
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 11 May 2025.
- Individual participant dataSharing planned: No
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lenalidomide and Methotrexate (MTX) in people with Cutaneous Lupus Erythematosus (CLE), run by Assistance Publique - Hôpitaux de Paris.
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 10 inclusion and 12 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 11 May 2025. 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 phase mean?
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?
Contact François CHASSET (+33156017225, francois.chasset@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients who achieve decrease of at least 50% from baseline in the CLASI activity (CLASI-A) score (time frame: At week 16). 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 11 May 2025.