Safety, Tolerability and Pharmacokinetics of MRG-106 in Patients With Mycosis Fungoides (MF), CLL, DLBCL or ATLL

November 19, 2020 updated by: miRagen Therapeutics, Inc.

A Phase 1 Dose-ranging Study to Investigate the Safety, Tolerability, and Pharmacokinetics of MRG-106 Following Local Intratumoral, Subcutaneous, and Intravenous Administration in Subjects With Various Lymphomas and Leukemias

Objectives of this clinical trial are to evaluate the safety, tolerability, pharmacokinetics and potential efficacy of the investigational drug, cobomarsen (MRG-106), in patients diagnosed with certain lymphomas and leukemias, including cutaneous T-cell lymphoma (CTCL) [mycosis fungoides (MF) subtype], chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL) [activated B-cell (ABC) subtype], and adult T-cell leukemia/lymphoma (ATLL). Cobomarsen is an inhibitor of a molecule called miR-155 that is found at high levels in these types of cancers and may be important in promoting the growth and survival of the cancer cells. Participants in the clinical trial will receive weekly doses of cobomarsen administered by injection under the skin or into a vein, or by injection directly into cancerous lesions in the skin (for CTCL only). Blood samples will be collected to measure how cobomarsen is processed by the body, and other measurements will be performed to study how normal and cancerous cells of the immune system respond when exposed to cobomarsen.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Study Design:

  • Part A: Cohorts of 3-6 patients diagnosed with MF will receive up to five intratumoral injections of cobomarsen over a period of up to 15 days with follow-up for an additional 20 days, beginning with the maximum deliverable intratumoral dose. Doses may be decreased in subsequent cohorts to determine the minimum pharmacodynamically active dose.
  • Parts B-F: Patients in these parts of the study will be diagnosed with MF (Parts B and C), CLL (Part D), DLBCL (Part E), or ATLL (Part F). All patients will receive subcutaneous or intravenous cobomarsen (or a combination of systemic and intratumoral administration for MF patients only) on Days 1, 3 and 5, and will continue dosing on a weekly schedule until the patient becomes intolerant, develops clinically significant side effects, progresses, or the trial is terminated. Doses administered will not exceed a dose level predicted to be safe based on all prior treatment experience with the drug. Patients in Part B may continue on a stable background therapy for their disease during their treatment with cobomarsen, while patients in Parts C-F will be treated with cobomarsen alone.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
66

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • City of Hope
      • La Jolla, California, United States, 92093
        • UCSD Moores Cancer Center
      • Los Angeles, California, United States, 90095
        • UCLA Department of Medicine
      • Orange, California, United States, 92868
        • Chao Family Comprehensive Cancer Center at University of California, Irvine
      • Stanford, California, United States, 94063
        • Stanford University Hospital and Clinics
    • Colorado
      • Aurora, Colorado, United States, 80045
        • University of Colorado, Anschutz Medical Campus
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Smilow Cancer Hospital at Yale-New Haven
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Sylvester Comprehensive Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern University; Department of Dermatology
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • New York
      • Bronx, New York, United States, 10467
        • Montefiore Medical Center, Albert Einstein College of Medicine
      • New York, New York, United States, 10065
        • Weill Cornell Medicine
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Ohio
      • Columbus, Ohio, United States, 43210
        • The Ohio State University Comprehensive Cancer Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19107
        • Thomas Jefferson University Hospital
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas MD Anderson Cancer Center
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Huntsman Cancer Institute
    • Virginia
      • Fairfax, Virginia, United States, 22003
        • Inova Melanoma and Skin Cancer Center / Inova Schar Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Parts A-C only: Patients must have biopsy proven MF, clinical stage I, II, or III (excluding visceral or nodal involvement), and must be refractory to or intolerant of established therapies for their condition
  • Part D only: Patients diagnosed with CLL who are intolerant to, or have disease that is relapsed/refractory after, at least two prior therapies
  • Part E only: Patients with biopsy-proven DLBCL who are intolerant to, or have disease that is relapsed/refractory after, at least two prior therapies, including any anti-CD20 monoclonal antibody and chemotherapy with curative intent
  • Part F only: Patients with documented HTLV-1 infection and histologically or cytologically proven ATLL of any stage, and who are intolerant to, or have disease that is relapsed/refractory after, at least one prior therapy
  • Females must not be pregnant or lactating. Women of child-bearing potential must use a highly effective method of contraception throughout their study participation and for at least 6 months following the last dose of study drug.
  • Males must be surgically sterile, abstinent, or if engaged in sexual relations with a female of child-bearing potential, must be willing to use a highly effective method of contraception throughout their study participation and for at least 6 months after the last dose of study drug.

Exclusion Criteria:

  • Evidence of renal or liver dysfunction at screening
  • Clinically significant anemia, neutropenia or thrombocytopenia at screening
  • History of bleeding diathesis or coagulopathy
  • Clinically significant cardiovascular disease, history of myocardial infarction within the last 6 months, or evidence of QTc interval prolongation at screening
  • Serologically positive for HIV; serologically positive for Hepatitis B or Hepatitis C with evidence of liver dysfunction or documented liver cirrhosis
  • Prior malignancies within the past 3 years (with allowance for adequately treated in situ carcinoma of the cervix uteri, and basal cell or localized squamous cell carcinoma of the skin treated with curative intent)
  • Use of an investigational small molecule drug during the 30 days prior to screening or use of an investigational oligonucleotide or biologic drug during the prior 90 days

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Part A, MF
Intratumoral Injection of cobomarsen
Drug: Cobomarsen
Other Names:
  • MRG-106
Experimental: Part B, MF
Subcutaneous, intravenous or a combination of systemic and intratumoral administration of cobomarsen with or without stable background therapy
Drug: Cobomarsen
Other Names:
  • MRG-106
Experimental: Part C, MF
Subcutaneous or intravenous administration of cobomarsen as monotherapy
Drug: Cobomarsen
Other Names:
  • MRG-106
Experimental: Part D, CLL
Subcutaneous or intravenous administration of cobomarsen as monotherapy
Drug: Cobomarsen
Other Names:
  • MRG-106
Experimental: Part E, DLBCL, activated B-cell (ABC) subtype
Subcutaneous or intravenous administration of cobomarsen as monotherapy
Drug: Cobomarsen
Other Names:
  • MRG-106
Experimental: Part F, ATLL
Subcutaneous or intravenous administration of cobomarsen as monotherapy
Drug: Cobomarsen
Other Names:
  • MRG-106

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Safety and tolerability of cobomarsen based on vital signs, physical examination, clinical laboratory tests, ECG, and incidence and severity of adverse events
Time Frame: From start of treatment to end of study participation
From start of treatment to end of study participation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Area under the plasma concentration vs. time curve (AUC) of cobomarsen following single and repeat doses administered intratumorally, subcutaneously or intravenously
Time Frame: Up to 56 days
Up to 56 days
Peak plasma concentration (Cmax) of cobomarsen following single and repeat doses administered intratumorally, subcutaneously or intravenously
Time Frame: Up to 56 days
Up to 56 days
Trough plasma concentration (Ctrough) of cobomarsen following each 4-week cycle of dosing
Time Frame: Monthly from Week 5 up to end of study participation
Monthly from Week 5 up to end of study participation
Skin disease severity (index lesions) - MF only
Time Frame: Every 2 weeks from start of treatment until end of study participation
Changes in MF skin lesion severity before and after treatment based on the Composite Assessment of Index Lesion Severity (CAILS) score
Every 2 weeks from start of treatment until end of study participation
Skin disease severity (whole body) - MF only
Time Frame: Every 2 weeks from start of treatment until end of study participation
Changes in MF skin lesion severity before and after treatment based on the modified Severity Weighted Assessment Tool (mSWAT) score
Every 2 weeks from start of treatment until end of study participation
Overall Response Rate in the skin - MF
Time Frame: Approximately 1 year
Proportion of subjects who achieve a partial response (PR) or complete response (CR) in the skin, based on SWAT score
Approximately 1 year
Overall Response Rate - CLL
Time Frame: Approximately 1 year
Proportion of subjects who achieve a PR or CR as defined by IWCLL criteria (Hallek et al., 2008) based on CT scans, bone marrow biopsies, and flow cytometry
Approximately 1 year
Minimal Residual Disease (MRD) - CLL only
Time Frame: Approximately 1 year
Proportion of subjects who achieve a CR with no evidence of MRD by flow cytometry
Approximately 1 year
Overall Response Rate - DLBCL
Time Frame: Approximately 1 year
Proportion of subjects who achieve a PR or CR as defined by the Lugano classification (Cheson et al., 2014) based on positron emission tomography-computed tomography (PET-CT) scans and bone marrow biopsy to confirm CR
Approximately 1 year
Overall Response Rate - ATLL
Time Frame: Approximately 1 year
Proportion of subjects who achieve a PR or CR as defined by international consensus criteria (Tsukasaki et al., 2009) based on CT scans and flow cytometry, and bone marrow biopsy to confirm CR
Approximately 1 year
Duration of Response
Time Frame: Up to approximately 2 years
Number of days from initial date of confirmed PR or CR until loss of response or relapse
Up to approximately 2 years
Time to Progression
Time Frame: Up to approximately 2 years
Number of days from first dose until objective disease progression
Up to approximately 2 years
Progression Free Survival (PFS)
Time Frame: Up to approximately 2 years
Number of days from first dose until objective disease progression or death from any cause
Up to approximately 2 years
Overall Survival (OS)
Time Frame: Up to approximately 2 years
Number of days from first dose until death from any cause
Up to approximately 2 years

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
miR-155-5p expression in cutaneous lesions of subjects with MF
Time Frame: At baseline and between Week 16 and end of study participation
Exploratory assessment based on quantitative real time polymerase chain reaction (qRT-PCR) analysis of total RNA isolated from skin biopsies
At baseline and between Week 16 and end of study participation
Proportion of neoplastic lymphoid cells in cutaneous lesions of subjects with MF
Time Frame: At baseline and between Week 16 and end of study participation
Exploratory histological assessment before and after treatment with cobomarsen
At baseline and between Week 16 and end of study participation
Proportions of immune cell subsets
Time Frame: At baseline and monthly or bimonthly, up to end of study participation
Exploratory assessment before and after treatment with cobomarsen by flow cytometry on whole blood
At baseline and monthly or bimonthly, up to end of study participation
Dermatology-specific quality of life - MF only
Time Frame: At baseline and monthly, up to approximately 2 years
Changes in skin-related quality of life based on the Skindex-29 assessment tool
At baseline and monthly, up to approximately 2 years
Pruritus - MF only
Time Frame: At baseline and monthly, up to approximately 2 years
Changes in intensity of skin itch based on the Pruritus Numerical Rating Scale
At baseline and monthly, up to approximately 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
miRagen Therapeutics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 9, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 6, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 6, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 15, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 16, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 20, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 23, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 19, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MRG106-11-101

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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