A Study to Evaluate the Effectiveness and Safety of Cobomarsen (MRG-106) vs. Active Comparator in Subjects with Mycosis Fungoides

Overview

About this study

The primary purpose of this study is to evaluate the effectiveness and safety of cobomarsen (also known as MRG-106) for the treatment of cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) subtype. Cobomarsen is designed to inhibit the activity of a molecule called miR-155 that may be important to the growth and survival of MF cancer cells. The study will compare the effects of cobomarsen to vorinostat, a drug that has been approved for the treatment of CTCL in the United States and several other countries.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Please contact the study team to discuss whether or not you are eligible to participate in a study.

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.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
  • Biopsy-proven CTCL, MF subtype.
  • Clinical stage IB, II, or III, with staging based on Screening assessments and following staging parameters set in this protocol.
  • Minimum mSWAT score of 10 at Screening.
  • Receipt of at least one prior therapy for CTCL (per National Comprehensive Cancer Network [NCCN] guidelines for generalized skin involvement; e.g., topical, phototherapy, total skin electron beam therapy [TSEBT], or systemic therapy.
  • Meets the following criteria per the central laboratory at Screening:
    • Calculated creatinine clearance ≥ 40 mL/min using 24-hour creatinine clearance OR modified Cockcroft-Gault equation (using ideal body mass [IBM] instead of mass);
    • AST and ALT ≤ 2.5 × the ULN; bilirubin ≤ 1.5 × ULN (except subjects with Gilbert’s Syndrome who may have bilirubin ≤ 3.0 × ULN following discussion with the Sponsor).
  • Females who had a menstrual cycle within 2 years of Screening must have a negative serum pregnancy test at Screening and a negative urine pregnancy test on their first dosing day.
  • Subjects of childbearing potential must agree to use highly effective methods of contraception.

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, defined as a documented history of B2 and/or B2 staging at the Screening visit. B2 means T-cell clone in peripheral blood + one of the following at Screening:
    • ≥ 1000 Sézary cells by direct examination; OR
    • ≥ 1000/μL CD4+ CD26; OR
    • ≥ 1000/μL CD4+ CD7.
  • Current evidence of large cell transformation (LCT), defined as > 25% of the lymphocytes at least 4 × the size of normal lymphocytes. Current evidence refers to LCT from biopsy performed within 4 months prior to randomization. Subjects with a history of LCT but with a negative current biopsy (within 4 months) are eligible, provided there is no clinical indication for chemotherapy.
  • 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. A subject with one or more enlarged lymph node(s) may be allowed, provided that a representative lymph node has been confirmed (via biopsy or positron emission tomography [PET]) scan) to be N0-N2 or SUV ≤ 5 within the 3 months prior to Day 1, and there has not been an appearance of new abnormal lymph nodes since the biopsy or PET scan. Subjects with uncharacterized enlarged lymph nodes (i.e. not confirmed by biopsy or PET scan) will not be allowed.
  • 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.
  • Recent history of alcoholism (within the past 1 year).
  • Known or suspected substance abuse within the past 1 year.
  • Unresolved toxicities from prior anticancer therapy, defined as having not resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, version 5.0), grade 0 or 1.
  • Receipt of any the following treatments:
    • Macrolide or tetracycline antibiotics within 28 days prior to Screening;
    • More than 3 short courses (≤ 7 days) 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 or radiotherapy 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.
    • Patients on chronic prophylactic (for prevention, more than 20 days per month) nonsteroidal antipruritic medications within 4 weeks of screening are excluded. Patients on symptomatic (for current symptoms) stable nonsteroidal antipruritic medications (dose and frequency remain the same for at least 1 month prior to screening) for symptomatic pruritus are allowed.
  • Positive test for blood (including trace) on urinalysis considered by the investigator to be consistent with undiagnosed clinically significant renal pathology requiring further investigation.
  • An active or uncontrolled infection defined as subjects who require systemic antibacterial, antiviral, or antifungal therapy within the last 7 days prior to Screening.
  • 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, per central laboratory. Subjects who are positive for Hepatitis C but have HCV RNA below the limit of quantitation, may be enrolled.
  • Clinically significant anemia (hemoglobin < 8 g/dL), neutropenia (absolute neutrophil count [ANC] < 1000/mm3) or thrombocytopenia (platelets < 50,000/mm^3) at Screening.
  • Bleeding diathesis or unstable coagulopathy within 2 years prior to 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.
  • Presence on ECG of QT interval corrected for heart rate using Fridericia’s formula (QTcF) > 450 msec for males or > 470 msec for females or > 480 msec for subjects with bundle branch block, based on a mean of the triplicate ECG measurements collected at Screening.
  • History of long QT syndrome and/or a history of persistent hypokalemia.
  • History of deep vein thrombosis and/or pulmonary embolism within 8 weeks of Screening.
  • Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or inability to communicate or cooperate fully with the Investigator.
  • Lactating or pregnant.
  • Major surgery within 4 weeks of first dose of study treatment.
  • 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.
  • Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).
  • Psychiatric illness, disability or social situation that would compromise the subject’s safety or ability to provide consent, or limit compliance with study requirements.
  • Clinically significant abnormalities in medical history, physical examination, or laboratory values, which, in the opinion of the Investigator, would make the subject unsuitable for inclusion in the study.
  • History of intolerance, or adverse or allergic reactions to oligonucleotide products and/or phosphate buffer solutions.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Jason Sluzevich, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Nabila Bennani, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Aaron Mangold, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20467305

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