Ritlecitinib in CTCL
- Conditions
- CTCLSezary SyndromeMycosis Fungoides
- Interventions
- Registration Number
- NCT05879458
- Lead Sponsor
- Icahn School of Medicine at Mount Sinai
- Brief Summary
The purpose of this research study is to evaluate the effectiveness and safety of Ritlecitinib in skin and blood in persons with Cutaneous T-Cell Lymphoma (CTCL). CTCL is a rare type of cancer that starts in the white blood cells and eventually can result in rashes or tumors in the skin. This study includes a 24 week Treatment Period and a 24 week Follow-up Period. This study will involve physical examinations, visual assessments, laboratory tests, PET-CT scans, electrocardiograms, photographs of your skin, skin biopsies, and hearing tests.
- Detailed Description
After providing informed consent, patients will be assessed for study eligibility at the Screening visit (day -28 to day -1) which includes: assessment of inclusion/exclusion criteria; targeted physical examination (including vital signs); mSWAT scoring and disease staging; electrocardiogram (ECG); review of medical history and concomitant medications as well as prior medications/treatments; and serum pregnancy test (if applicable). Laboratory tests will be performed for Complete Blood Count (CBC) with differentials (basophils, eosinophils, lymphocytes, monocytes, neutrophils), serum chemistry including albumin, alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), creatinine, creatine kinase, potassium, sodium, total bilirubin, LDH, viral surveillance panel (EBV, CMV, HSV1, HSV2, and VZV), as well as hepatitis B surface antigen (HBsAg), HBcAb, hepatitis C antibody, and undergo testing for human immunodeficiency virus (HIV). Urinalysis will be performed. Patients will also undergo tuberculin purified protein derivative (PPD) or QuantiFERON TB-Gold test (QFT) testing. Patients will also undergo flow cytometric analyses and TCR rearrangement studies of peripheral blood to monitor potential CTCL blood involvement. CT scans with PET (positron emission tomography) scans will be performed within 4 weeks before baseline to help establish or confirm peripheral lymph node size and assign TNM classification, or at any time if internal involvement is suspected by the investigator.
Patients who meet eligibility criteria (meeting all inclusion and no exclusion criteria) will undergo Baseline / Day 0 assessments. These assessments include vital signs and targeted physical examination, mSWAT scoring, clinical disease staging, questionnaires, clinical photography, urine pregnancy test (if applicable), and blood collection for chemistry, hematology, mechanistic studies, baseline for drug levels, blood DNA analysis, blood RNA analysis, and blood proteomic analysis. Two skin biopsies will be obtained (one from an involved area and one from an adjacent uninvolved area). Concomitant medications and any adverse events will be assessed.
Patients will then receive the first oral dose (200mg) of ritlecitinib. Patients will continue to receive the study drug QD through Week 24.
Patients will return for visits every 2-4 weeks to have the following performed: vital signs and targeted physical will be taken; concomitant medications and any adverse events will be assessed.
Safety, laboratory, and clinical assessments, as well as questionnaires will be performed at specified clinic visits. A serum pregnancy test will be performed at Screening and urine pregnancy tests will be performed at Baseline and every 2-4 weeks prior to administration of the study drug, if applicable. Clinical photographs of the skin lesions will be taken at each visit.
Skin biopsies will be performed on all patients at Baseline and Week 24 or Early Termination visit. At Baseline, biopsies will be obtained from involved and uninvolved areas of a CTCL lesion. At Week 24 or Early Termination visit, the biopsy will be performed in the vicinity of the involved area biopsied at Baseline. An optional biopsy will be performed at Week 12, within the same area that was biopsied at Baseline.
At Baseline, serum will be obtained for DNA (1 PaxGene), RNA (2 PaxGene), and proteomic analysis (2 tubes serum). Studies of RNA and proteomic analysis will further be performed at Weeks 12, 24 and 48/early termination.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 7
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Arm Ritlecitinib Open-Label Ritlecitinib
- Primary Outcome Measures
Name Time Method Change in Modified Severity Weighted Assessment Tool (mSWAT) Baseline and Week 24 Change in Modified Severity Weighted Assessment Tool (mSWAT) at Week 24 from baseline. Skin response was primarily classified based on an assessment using mSWAT, provided there was documented evidence of stable disease or better in lymph node/viscera.The mSWAT is a tool specifically developed to evaluate the extent of skin disease in CTCL.
Responses in the skin based on SWAT are defined as:
Complete Response (CR): no evidence of skin disease Partial Response (PR): ≥ 50% decrease of the modified SWAT score compared with baseline Stable Disease (SD): Neither CR, PR, or PD as compared with baseline, i.e. change from baseline is less than a 50% decrease but also less than a 25 % increase in the modified SWAT score Progressive Disease (PD): ≥ 25% increase in the modified SWAT score compared with baseline.
- Secondary Outcome Measures
Name Time Method Change in Modified Severity Weighted Assessment Tool (mSWAT) Baseline and at each visit from week 2 to week 48 / EOS except for week 24 Change in Modified Severity Weighted Assessment Tool (mSWAT) at each visit from baseline. Skin response was primarily classified based on an assessment using mSWAT, provided there was documented evidence of stable disease or better in lymph node/viscera.The mSWAT is a tool specifically developed to evaluate the extent of skin disease in CTCL.
Responses in the skin based on SWAT are defined as:
Complete Response (CR): no evidence of skin disease Partial Response (PR): ≥ 50% decrease of the modified SWAT score compared with baseline Stable Disease (SD): Neither CR, PR, or PD as compared with baseline, i.e. change from baseline is less than a 50% decrease but also less than a 25 % increase in the modified SWAT score Progressive Disease (PD): ≥ 25% increase in the modified SWAT score compared with baseline.Treatment Emergent Adverse Events up to Week 48/EOS Incidence and severity of treatment-emergent adverse events
Number of Serious Adverse Events up to Week 48/EOS Number of serious adverse events (SAE) leading to discontinuation
Number of Adverse Events up to Week 48/EOS Number of Adverse events (AE) leading to discontinuation
Number of clinically significant abnormalities in vital signs up to Week 48/EOS Number of clinically significant abnormalities in any vital signs
Number of clinically significant abnormalities in clinical laboratory values up to Week 48/EOS Number of clinically significant abnormalities in any clinical laboratory values
Change in Percentage of patients achieving 50% or greater improvement in mSWAT score Baseline and at each visit from week 2 to week 48 / EOS Change in Percentage of patients achieving 50% or greater improvement in mSWAT score (mSWAT50) at every visit as compared to baseline.
Skin response was primarily classified based on an assessment using mSWAT, provided there was documented evidence of stable disease or better in lymph node/viscera.The mSWAT is a tool specifically developed to evaluate the extent of skin disease in CTCL.
Responses in the skin based on SWAT are defined as:
Complete Response (CR): no evidence of skin disease Partial Response (PR): ≥ 50% decrease of the modified SWAT score compared with baseline Stable Disease (SD): Neither CR, PR, or PD as compared with baseline, i.e. change from baseline is less than a 50% decrease but also less than a 25 % increase in the modified SWAT score Progressive Disease (PD): ≥ 25% increase in the modified SWAT score compared with baseline.Change in Global Response Score Baseline and at each visit from week 2 to week 48 / EOS Change in Global Response Score at each vist as compared to baseline.
Percentage of patients achieving complete response (CR: 100% improvement), partial response (PR: 50% to 99% reduction from the baseline score), stable disease (SD: \<25% increase to \<50% clearance from baseline), and progressive disease (\>25% worsening above the baseline score) in skinAbsolute change of health-related quality of life (Skindex-29) Baseline and at each visit from week 2 to week 48 / EOS Absolute change of health-related quality of life (Skindex-29 - questionnaire regarding skin conditions) from Baseline up to Week 48.
Skindex29 is a 30 question survey that measures quality of life. It is scored from 1-Never to 5-All the time. Full scale from 30-150. The lower the score, the better the quality of life.Absolute change of health-related quality of life (FACT-G) Baseline and at each visit from week 2 to week 48 / EOS Absolute change of health-related quality of life (FACT-G - questionnaire regarding Physical/Social/Family well being) from Baseline up to Week 48.
The FACT-G is comprised of four subscales: physical well-being (7-items, score range 0-28), social/family well-being (7-items, score range 0-28), emotional well-being (6-items, score range 0-24), and functional well-being (7-items, score range 0-28). All questions in the FACT-G use a 5-point rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a bit; and 4 = Very much). Full scale scored from 0-108. The higher the score, the better the quality of life.Absolute change of IPQ-R (Illness perception questionnaire) Baseline and at each visit from week 2 to week 48 / EOS Absolute change of IPQ-R (Illness perception questionnaire) from Baseline up to Week 48.
The IPQ-R an 70-item instrument developed to provide a quantitative measurement of the components of illness representations. It is divided into three sections: identity subscale (14 symptoms scored as 1-yes or 0-no, subscale from 0-14), views about illness (38 questions scored between 5-strongly agree to 1-strongly disagree, subscale from 38-190) and a third section regarding views on possible causes (18 causes scored between 5-strongly agree to 1-strongly disagree, subscale from 18-90).
Full scale from 56-294. High scores on the identity and views of illness sections represent strongly held beliefs about the number of symptoms attributed, the negative consequences, and the chronicity and cyclical nature of the illness. High scores in the section regarding causes represent positive beliefs about controllability and a personal understanding of the illness.Percentage change of pruritus according to visual analogue scale (VAS) Baseline and at each visit from week 2 to week 48 / EOS Percentage change of pruritus according to visual analogue scale (VAS). Line graph to collect information about general itch level as well as worst itch level in the past 24 hours on a scale of 0 to 10, with higher score indicating more itch from baseline up to week 48.
Trial Locations
- Locations (1)
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States