Cutaneous T-Cell Lymphoma (CTCL), Mycosis Fungoides (MF) Subtype MedDRA version: 20.0 Level: PT Classification code 10028483 Term: Mycosis fungoides System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
miRagen Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Must provide written informed consent (signed and dated) and any authorizations required by law and be able to comply with all study requirements. • Males or females, = 18 years of age at the time of informed consent. • Biopsy-proven CTCL, MF subtype. • Clinical stage IB, II, or III, with staging based on Screening assessments. • Minimum mSWAT score of 10 at Screening. • Receipt of at least one prior therapy for CTCL (per the National Comprehensive Cancer Network [NCCN] guidelines for generalized skin involvement; e.g., topical, phototherapy, Total Skin Electron Beam Therapy [TSEBT] or systemic therapy). • Subjects of childbearing potential must agree to use highly effective methods of contraception as defined in the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 63 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 63
Exclusion criteria
Exclusion criteria: • Previous enrollment in a cobomarsen study. • Prior therapy with vorinostat or other HDAC inhibitors, or contraindication to an HDAC inhibitor. • Sézary syndrome or mycosis fungoides with B2 involvement. • Evidence of large cell transformation • Evidence of enlarged peripheral or central lymph node(s) > 1.5 cm in the long diameter or > 1.0 cm in the short diameter by radiographical imaging at Screening. • Any palpable peripheral node, regardless of size, that on physical examination is firm, irregular, clustered, or fixed, unless histologically confirmed to be non-malignant. • Evidence of visceral involvement related to MF at Screening. • Receipt of any the following treatments: - Macrolide or tetracycline antibiotics within 28 days prior to Screening; - More than 3 short courses of prednisone equivalent > 10 mg per day within 8 weeks prior to Screening; however, a stable regimen of systemic prednisone equivalent to = 10 mg per day (or steroid equivalent) is permitted; - Total skin electron beam therapy within 4 weeks prior to Screening; - Investigational small molecule drug within 5 half-lives prior to Screening; - Investigational biologic drug within 5 half-lives prior to Screening; - Phototherapy within 4 weeks prior to Screening; - Antibody-directed or immunoglobulin-based immune therapy or other monoclonal antibody therapies within 8 weeks prior to Screening; - Previous chronic (more than 20 days total) high potency topical corticosteroid use within 4 weeks of Screening. Stable doses of low to medium potency topical corticosteroids are allowed; - Previous chronic (more than 20 days total) use of topical MF treatments (not listed in the bullets above) within 4 weeks prior to Screening; - Previous systemic MF treatments (not listed in the bullets above) within 4 weeks prior to Screening; - Previous treatment with an oligonucleotide. • Clinically significant liver disease within 1 year prior to Screening. • Positivity for human immunodeficiency virus (HIV), Hepatitis B surface antigen, or Hepatitis C at the time of Screening, • Clinically significant anemia, neutropenia or thrombocytopenia at Screening. • Previous or concurrent malignancy with the following exceptions: - Adequately treated basal cell or squamous cell carcinoma of the skin (adequate wound healing is required prior to study entry), - In situ carcinoma of the cervix, treated curatively and without evidence of recurrence for at least 3 years prior to the study, - Or other solid tumor treated curatively, and without evidence of recurrence for at least 3 years prior to study entry. • History of long QT syndrome and/or a history of persistent hypokalemia • Lactating or pregnant. • Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure, as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to enrollment. • History of stroke or intracranial hemorrhage within 6 months prior to enrollment. • Clinically significant abnormalities which, in the opinion of the Investigator, would make subject unsuitable for inclusion in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the trial is to evaluate the efficacy of cobomarsen in subjects with MF.;Secondary Objective: • Investigate the safety and tolerability of cobomarsen in subjects with MF. • Characterize the population pharmacokinetics (PK) of cobomarsen in subjects with MF.;Primary end point(s): Primary Efficacy Evaluation: Proportion of subjects achieving an objective response (complete response [CR] or partial response [PR]) of at least 4 months duration (ORR4) using composite global response criteria, including radiological imaging, flow cytometry, and the Modified Severity Weighted Assessment Tool (mSWAT) scoring.;Timepoint(s) of evaluation of this end point: Global response criteria collected 4 weeks after 4 months of sustained response (PR or CR) in the skin, and every 12 weeks thereafter. | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Progression free survival, time to progression, overall survival, complete response rate: assessed throughout study Daily pruritus and pain score from Day 1 until follow up visit. Skindex-29, mSWAT: every 4 weeks to week 81, every 8 weeks thereafter Safety and tolerability: assessed throughout study PK: Days 1, 2, 3, 5, 8, 15, 29, every 4 weeks through week 81 and every 8 weeks thereafter.;Secondary end point(s): Efficacy measures • Key Secondary Endpoint: Progression-free survival (PFS). • Change from baseline and longitudinally during the study in Pruritus Numerical Rating Scale (NRS). • Change from baseline and longitudinally during the study in Skindex-29 total score. • Change from baseline and longitudinally during the study in Skindex-29 Subdomains (Symptoms, Emotion and Functionality). • Change from baseline and longitudinally during the study in Pain NRS. • Difference in drug tolerability by Patient Impression of Treatment Side Effects • Duration of composite global response for responding subjects. • Complete response rate (CRR). • Time to progression (TTP). • Time to maximal effect in mSWAT. • Proportion of subjects achieving = 50% improvement in mSWAT of at least 4-months duration. • Proportion of subjects achieving = 50% improvement in mSWAT of at least 28-days duration. • Percent of subjects achieving = 50% improvement in mSWAT from baseline at 28 days and at 4 months. • Time to = 50% improvement in mSWAT. • Duration of response in skin (no progression after achieving = 50% improvement in mSWAT). • Change in pruritus medication utilization from baseline and incidence of pruritus medication utilization. • Overall survival. • Time to next treatment. Safety and Tolerability Evaluations: • Incidence and severity of clinically significant adverse events (AEs) (including grade 3 and 4 AEs, treatment-related AEs, serious adverse events [SAEs], and AEs requiring discontinuation), physical examination findings, chan | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactSOLAR Clinical Trial Information
miRagen Therapeutics, Inc.
Outcome results
None listed