Cutaneous Lupus Erythematosus (CLE)
Conditions
Keywords
Cutaneous Lupus Erythematosus, CLE, lenalidomide, revlimid, thalidomide derivative, drug, lupus
Brief summary
This study is being conducted to evaluate the safety and effectiveness of lenalidomide (Revlimid®) in subjects with Cutaneous Lupus Erythematosus (CLE). The study drug will be used in an off-label indication to treat 6 subjects for 12 months each. Men and women over the age of 18, who have a biopsy proven diagnosis of CLE and who have failed standard treatment, will be included in the study.
Detailed description
Cutaneous lupus erythematosus (CLE) is a chronic and often disabling disease which affects the skin. Many patients experience scarring and inflammation of the skin, which often occur on the face. Moderate to severe CLE is most frequently treated with antimalarial drugs such as hydroxychloroquine, quinacrine or chloroquine. Up to 70% of CLE patients treated with antimalarials experience a beneficial clinical response, while the remainder of patients show no response or continue to experience progression of the disease. Thalidomide has been used successfully in such patients, with up to 75% clinical response rate in refractory CLE patients. However, thalidomide is a known teratogen and can cause severe birth defects, including short, malformed limbs and damage to peripheral nerves in the extremities, requiring patients to be monitored for pregnancy. In addition, up to 25% of patients on thalidomide develop peripheral neuropathy. A new drug, lenalidomide (REVLIMID®), an analogue of thalidomide, has been developed to treat neoplastic and inflammatory conditions, including various oncologic conditions such as multiple myeloma, myelodysplastic syndrome and solid tumors. Unlike thalidomide, lenalidomide (REVLIMID®) is not known to cause the extent of serious side effects caused by thalidomide; however, it must also be monitored for side effects and be distributed under the RevAssist program authorized by the drug manufacturer, Celgene Corporation. The primary goal of this investigator-initiated, small pilot study is to evaluate the safety and effectiveness of lenalidomide (REVLIMID®) in CLE subjects using measurements such as the CLASI (Cutaneous Lupus Activity and Severity Index). The study drug will be used in an off-label indication to treat 6 subjects, for whom lenalidomide (REVLIMID®) will be provided at no cost by the drug manufacturer. Men and women over the age of 18, who have a biopsy proven diagnosis of refractory CLE and who have failed standard treatment with hydroxychloroquine for up to three months, will be included in the study. Secondarily, the study will evaluate the biologic effects of lenalidomide on pathogenic and immunologic mechanisms of the CLE disease process during the treatment period by collecting skin specimens (biopsies) and blood samples.
Interventions
DRUGLenalidomide
Sponsors
Celgene Corporation
University of Pennsylvania
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must understand and voluntarily sign Informed Consent and HIPAA forms. * Males and females over the age of 18 at the time of signing informed consent form. * Able to adhere to the study visit schedule and other protocol requirements * Subjects must have biopsy proven Cutaneous Lupus Erythematosus (CLE) either in the form of Discoid Lupus Erythematosus (DLE) or Subacute Lupus Erythematosus (SCLE), with or without systemic involvement. * Subjects must have grade II erythema in at least three skin locations as defined by the Cutaneous Lupus Activity and Severity Index (CLASI). * Subjects must have failed standard treatment with hydroxychloroquine (Plaquenil) for up to three months. * Female subjects who are not pregnant. * Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional method AT THE SAME TIME, at least 28 days before starting to take lenalidomide (Revlimid®). FCBP must also agree to ongoing pregnancy testing. Males must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure. * If pregnancy or a positive pregnancy test is noted in a study subject or in the partner of a male study subject during study participation, the study drug must be discontinued immediately.
Exclusion criteria
* Any serious medical condition, laboratory abnormality or psychiatric illness that would prevent the subject from signing the informed consent form. * Female subjects who are pregnant, plan to be pregnant during the study, or who are breastfeeding. * Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk for study participation, or confounds the ability to interpret data from the study. * Use of any other experimental drug or therapy within 28 days of baseline. * Known hypersensitivity to thalidomide. * The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs. * Prior history of deep vein thrombosis (DVT). * Prior history of pulmonary embolus (PE). * Known positive for HIV viral DNA by qPCR. * Positive hepatitis B surface antigen, or hepatitis C. * Platelet count \< 50,000/mcL. * Absolute neutrophil count \< 750/mcL * Lymphopenia \< 500/mcL. * Have current signs or symptoms of severe progressive or uncontrolled renal disease (creatinine ≥1.5 x ULN). * If female, unwillingness to use one highly effective method and one additional method of birth control. * If male, unwillingness to use a latex condom during intercourse with females of childbearing potential. * Continued therapy with thalidomide.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cutaneous Lupus Area and Severity Index (CLASI) | Weeks 0 through 52 | The Cutaneous Lupus Area and Severity Index (CLASI); range of disease activity is 0-70. Lower scores reflect less activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physician Global Assessment (PGA) for Skin | Weeks 0 through 52 | General skin scores were recorded on a 10 cm visual analogue scale at each visit. At each visit on scale 0-10, 0 corresponding to worst skin condition imaginable and 10 to perfect health. |
| Patient General Assessment (PtGA) for Skin | Weeks 0 through 52 | General skin scores were recorded by the patient on a 10 cm visual analogue scale at each visit by the patient. At each visit on scale 0-10, 0 corresponding to worst skin condition imaginable and 10 to perfect health. |
| Pain in Skin | Weeks 0 through 52 | Pain in skin was recorded on a 10 cm visual analogue scale at each visit by the patient. At each visit on scale 0-10, 0 corresponding to no pain and 10 to pain as bad as you can imagine. |
| Number of Participants With Change in IFN and CD4 Levels at 6 Weeks | 6 weeks | CXCL10, an interferon-inducible chemokine, and immunophenotyping by immunostaining. Measurement of interferon-inducible genes from peripheral blood mononuclear cells before and after treatment. |
| Fatigue | Weeks 0 through 52 | Fatigue scores were recorded on a 10 cm visual analogue scale at each visit by the patient. At each visit on scale 0-10, 0 corresponding to no fatigure and 10 to fatigue as bad as you can imagine. |
| Skindex Symptoms | Weeks 0 through 52 | Skindex symptoms scores are scored 1-5 and then normalized to 100, with a higher score corresponding to a worse impression. The absence of symptom impact on QoL is scored as 20 (this is represented as a 1 on the 1-5 scale. The worst impact of symptoms on QoL is 100. This is represented as a 5 on the 1-5 scale. |
| Skindex Function | Weeks 0 through 52 | Skindex function scores are scored 1-5 and then normalized to 100, with a higher score corresponding to a worse impression. The absence of function impact on QoL is scored as 20 (this is represented as a 1 on the 1-5 scale. The worst impact of function on QoL is 100. This is represented as a 5 on the 1-5 scale. |
| Itch in Skin | Weeks 0 through 52 | Itch scores were recorded on a 10 cm visual analogue scale at each visit by the patient. At each visit on scale 0-10, 0 corresponding to no itch and 10 to itch as bad as you can imagine. |
Countries
United States
Participant flow
Pre-assignment details
The sample size was determined by the number of study subjects for whom Celgene Corporation was willing to supply medication during and beyond the study period. It was felt that 5 study subjects would provide valuable information about the responsiveness of severe CLE to lenalidomide (REVLIMID®) and subjects' tolerability to the study medication.
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide Patients took 5 mg daily of oral lenalidomide for the initial 6 weeks. Patients who had responded at 6 weeks lowered their dose to 5 mg every other day, while non-responders were increased to a dose of 10 mg daily. | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 2 |
Baseline characteristics
| Characteristic | Lenalidomide |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 40.8 years STANDARD_DEVIATION 4.82 |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Cutaneous Lupus Area and Severity Index (CLASI)
The Cutaneous Lupus Area and Severity Index (CLASI); range of disease activity is 0-70. Lower scores reflect less activity.
Time frame: Weeks 0 through 52
Population: Two patients were not included at week 52 because one did not respond and one had new onset proteinuria and arthralgias.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Lenalidomide | Cutaneous Lupus Area and Severity Index (CLASI) | 0 weeks | 21.4 units on a scale |
| Lenalidomide | Cutaneous Lupus Area and Severity Index (CLASI) | 6 weeks | 10.8 units on a scale |
| Lenalidomide | Cutaneous Lupus Area and Severity Index (CLASI) | 12 weeks | 8.6 units on a scale |
| Lenalidomide | Cutaneous Lupus Area and Severity Index (CLASI) | 52 weeks | 5.3 units on a scale |
Secondary
Fatigue
Fatigue scores were recorded on a 10 cm visual analogue scale at each visit by the patient. At each visit on scale 0-10, 0 corresponding to no fatigure and 10 to fatigue as bad as you can imagine.
Time frame: Weeks 0 through 52
Population: 5 patients until week 12, 3 patients to week 52. Dropout prevented proper analysis of week 12 to 52.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Lenalidomide | Fatigue | week 0 | 7.25 units on a scale |
| Lenalidomide | Fatigue | week 6 | 3.4 units on a scale |
| Lenalidomide | Fatigue | week 12 | 5.25 units on a scale |
| Lenalidomide | Fatigue | week 52 | 3 units on a scale |
Secondary
Itch in Skin
Itch scores were recorded on a 10 cm visual analogue scale at each visit by the patient. At each visit on scale 0-10, 0 corresponding to no itch and 10 to itch as bad as you can imagine.
Time frame: Weeks 0 through 52
Population: 5 patients until week 12, 3 patients to week 52. Dropout prevented proper analysis of week 12 to 52.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Lenalidomide | Itch in Skin | week 0 | 4.0 units on a scale |
| Lenalidomide | Itch in Skin | week 6 | 1.2 units on a scale |
| Lenalidomide | Itch in Skin | week 12 | 2.25 units on a scale |
| Lenalidomide | Itch in Skin | week 52 | 0 units on a scale |
Secondary
Number of Participants With Change in IFN and CD4 Levels at 6 Weeks
CXCL10, an interferon-inducible chemokine, and immunophenotyping by immunostaining. Measurement of interferon-inducible genes from peripheral blood mononuclear cells before and after treatment.
Time frame: 6 weeks
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lenalidomide | Number of Participants With Change in IFN and CD4 Levels at 6 Weeks | IFN score decrease | 4 Participants |
| Lenalidomide | Number of Participants With Change in IFN and CD4 Levels at 6 Weeks | CD4 decrease | 4 Participants |
| Lenalidomide Nonresponder | Number of Participants With Change in IFN and CD4 Levels at 6 Weeks | IFN score decrease | 1 Participants |
| Lenalidomide Nonresponder | Number of Participants With Change in IFN and CD4 Levels at 6 Weeks | CD4 decrease | 1 Participants |
Secondary
Pain in Skin
Pain in skin was recorded on a 10 cm visual analogue scale at each visit by the patient. At each visit on scale 0-10, 0 corresponding to no pain and 10 to pain as bad as you can imagine.
Time frame: Weeks 0 through 52
Population: 5 patients until week 12, 3 patients to week 52. Dropout prevented proper analysis of week 12 to 52.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Lenalidomide | Pain in Skin | week 0 | 4.5 units on a scale |
| Lenalidomide | Pain in Skin | week 6 | 2 units on a scale |
| Lenalidomide | Pain in Skin | week 12 | 2.5 units on a scale |
| Lenalidomide | Pain in Skin | week 52 | 0.5 units on a scale |
Secondary
Patient General Assessment (PtGA) for Skin
General skin scores were recorded by the patient on a 10 cm visual analogue scale at each visit by the patient. At each visit on scale 0-10, 0 corresponding to worst skin condition imaginable and 10 to perfect health.
Time frame: Weeks 0 through 52
Population: 5 patients until week 12, 3 patients to week 52. Dropout prevented proper analysis of week 12 to 52.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Lenalidomide | Patient General Assessment (PtGA) for Skin | week 0 | 5.6 units on a scale |
| Lenalidomide | Patient General Assessment (PtGA) for Skin | week 6 | 3.6 units on a scale |
| Lenalidomide | Patient General Assessment (PtGA) for Skin | week 12 | 4.2 units on a scale |
| Lenalidomide | Patient General Assessment (PtGA) for Skin | week 52 | 0.8 units on a scale |
Secondary
Physician Global Assessment (PGA) for Skin
General skin scores were recorded on a 10 cm visual analogue scale at each visit. At each visit on scale 0-10, 0 corresponding to worst skin condition imaginable and 10 to perfect health.
Time frame: Weeks 0 through 52
Population: 5 patients until week 12, 3 patients to week 52. Dropout prevented proper analysis of week 12 to 52.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Lenalidomide | Physician Global Assessment (PGA) for Skin | week 0 | 6 units on a scale |
| Lenalidomide | Physician Global Assessment (PGA) for Skin | week 6 | 3 units on a scale |
| Lenalidomide | Physician Global Assessment (PGA) for Skin | week 12 | 3.8 units on a scale |
| Lenalidomide | Physician Global Assessment (PGA) for Skin | week 52 | 2 units on a scale |
Secondary
Skindex Function
Skindex function scores are scored 1-5 and then normalized to 100, with a higher score corresponding to a worse impression. The absence of function impact on QoL is scored as 20 (this is represented as a 1 on the 1-5 scale. The worst impact of function on QoL is 100. This is represented as a 5 on the 1-5 scale.
Time frame: Weeks 0 through 52
Population: 5 patients until week 12, 3 patients to week 52. Dropout prevented proper analysis of week 12 to 52.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Lenalidomide | Skindex Function | week 0 | 41.26 units on a scale |
| Lenalidomide | Skindex Function | week 6 | 30.42 units on a scale |
| Lenalidomide | Skindex Function | week 12 | 29.2 units on a scale |
| Lenalidomide | Skindex Function | week 52 | 4.2 units on a scale |
Secondary
Skindex Symptoms
Skindex symptoms scores are scored 1-5 and then normalized to 100, with a higher score corresponding to a worse impression. The absence of symptom impact on QoL is scored as 20 (this is represented as a 1 on the 1-5 scale. The worst impact of symptoms on QoL is 100. This is represented as a 5 on the 1-5 scale.
Time frame: Weeks 0 through 52
Population: 5 patients until week 12, 3 patients to week 52. Dropout prevented proper analysis of week 12 to 52.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Lenalidomide | Skindex Symptoms | week 0 | 58.5 units on a scale |
| Lenalidomide | Skindex Symptoms | week 6 | 41.82 units on a scale |
| Lenalidomide | Skindex Symptoms | week 12 | 36.4 units on a scale |
| Lenalidomide | Skindex Symptoms | week 52 | 12.5 units on a scale |