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Trial record 1 of 1 for:    MRG106
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Safety, Tolerability and Pharmacokinetics of MRG-106 in Patients With Mycosis Fungoides (MF), CLL, DLBCL or ATLL

This study is currently recruiting participants.
Verified November 2017 by miRagen Therapeutics, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02580552
First Posted: October 20, 2015
Last Update Posted: November 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
miRagen Therapeutics, Inc.
  Purpose
Objectives of this clinical trial are to evaluate the safety, tolerability, pharmacokinetics and potential efficacy of the investigational drug, 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), and adult T-cell leukemia/lymphoma (ATLL). MRG-106 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 MRG-106 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 MRG-106 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 MRG-106.

Condition Intervention Phase
Cutaneous T-cell Lymphoma (CTCL) Mycosis Fungoides (MF) Chronic Lymphocytic Leukemia (CLL) Diffuse Large B-Cell Lymphoma (DLBCL) Adult T-Cell Leukemia/Lymphoma (ATLL) Drug: MRG-106 Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by miRagen Therapeutics, Inc.:

Primary Outcome Measures:
  • Safety and tolerability of MRG-106 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 ]

Secondary Outcome Measures:
  • Area under the plasma concentration vs. time curve (AUC) of MRG-106 following single and repeat doses administered intratumorally, subcutaneously or intravenously [ Time Frame: Up to 56 days ]
  • Peak plasma concentration (Cmax) of MRG-106 following single and repeat doses administered intratumorally, subcutaneously or intravenously [ Time Frame: Up to 56 days ]
  • Trough plasma concentration (Ctrough) of MRG-106 following each 4-week cycle of dosing [ Time Frame: 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

  • 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

  • Overall Response Rate - MF [ Time Frame: Approximately 1 year ]
    Proportion of subjects who achieve a partial response (PR) or complete response (CR) as defined by international consensus criteria (Olsen et al., 2011), based on SWAT score and confirmed by computed tomography (CT) scan and flow cytometry

  • 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

  • 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

  • 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

  • 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., 2008) based on CT scans and flow cytometry, and bone marrow biopsy to confirm CR

  • 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

  • Time to Progression [ Time Frame: Up to approximately 2 years ]
    Number of days from first dose until objective disease progression

  • 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

  • Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
    Number of days from first dose until death from any cause


Other Outcome Measures:
  • 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

  • Proportion of CD4+ 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 MRG-106

  • 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 MRG-106 by flow cytometry on whole blood


Estimated Enrollment: 75
Actual Study Start Date: February 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part A, MF
Intratumoral Injection of MRG-106
Drug: MRG-106
Experimental: Part B, MF
Subcutaneous, intravenous or a combination of systemic and intratumoral administration of MRG-106 with stable background therapy
Drug: MRG-106
Experimental: Part C, MF
Subcutaneous or intravenous administration of MRG-106 as monotherapy
Drug: MRG-106
Experimental: Part D, CLL
Subcutaneous or intravenous administration of MRG-106 as monotherapy
Drug: MRG-106
Experimental: Part E, DLBCL
Subcutaneous or intravenous administration of MRG-106 as monotherapy
Drug: MRG-106
Experimental: Part F, ATLL
Subcutaneous or intravenous administration of MRG-106 as monotherapy
Drug: MRG-106

Detailed Description:

Study Design:

  • Part A: Cohorts of 3-6 patients diagnosed with MF will receive up to five intratumoral injections of MRG-106 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 MRG-106 (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 MRG-106, while patients in Parts C-F will be treated with MRG-106 alone.
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02580552


Contacts
Contact: miRagen Therapeutics, Inc. 720-407-4603

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Jaemee Bautista    626-218-3033    jbautista@coh.org   
Principal Investigator: Christiane Querfeld, MD         
UCSD Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Contact: Natalie McCarthy, MA    858-822-0743    nmccarthy@ucsd.edu   
Principal Investigator: Thomas Kipps, MD, PhD         
UCLA Department of Medicine Recruiting
Los Angeles, California, United States, 90095
Contact: Jonsson Comprehensive Cancer Center Clinical Research Unit    310-794-6500      
Principal Investigator: Herbert Eradat, MD         
Chao Family Comprehensive Cancer Center at University of California, Irvine Recruiting
Orange, California, United States, 92868
Contact    877-827-8839    ucstudy@uci.edu   
Principal Investigator: Lauren Pinter-Brown, MD         
Stanford University Hospital and Clinics Recruiting
Stanford, California, United States, 94063
Contact: Zachary Hopkins    650-421-6370    zehop@stanford.edu   
Principal Investigator: Youn Kim, MD         
United States, Colorado
University of Colorado, Anschutz Medical Campus Recruiting
Aurora, Colorado, United States, 80045
Contact: Rachael Wax    720-848-9384    rachael.wax@ucdenver.edu   
Principal Investigator: Theresa R. Pacheco, MD         
United States, Connecticut
Smilow Cancer Hospital at Yale-New Haven Recruiting
New Haven, Connecticut, United States, 06510
Contact: Laura Leary    203-737-8884    laura.leary@yale.edu   
Principal Investigator: Francine Foss, MD         
United States, Illinois
Northwestern University; Department of Dermatology Recruiting
Chicago, Illinois, United States, 60611
Contact: Linda Serrano    312-503-5900    linda.serrano@northwestern.edu   
Principal Investigator: Joan Guitart, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Not yet recruiting
New York, New York, United States, 10065
Contact: Alison Moskowitz, MD    212-639-4839    moskoia@mskcc.org   
Principal Investigator: Alison Moskowitz, MD         
United States, Ohio
The Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210
Contact: Juliana Engleman    614-685-6005    Juliana.Engleman@osumc.edu   
Principal Investigator: Basem William, MD         
United States, Pennsylvania
Thomas Jefferson University Hospital Not yet recruiting
Philadelphia, Pennsylvania, United States, 19107
Contact: Sophia Hines    215-955-0030    Sophia.hines@jefferson.edu   
Principal Investigator: Pierluigi Porcu, MD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Lisa Arriaga    713-794-1447    larriaga@mdanderson.org   
Principal Investigator: Auris Huen, MD         
United States, Utah
Huntsman Cancer Institute Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Ahmad Halwani, MD    801-581-4477    clinical.trials@hci.utah.edu   
Principal Investigator: Ahmad Halwani, MD         
United States, Virginia
Inova Melanoma and Skin Cancer Center / Inova Schar Cancer Institute Recruiting
Fairfax, Virginia, United States, 22003
Contact: Kelly Jeffords, CCRC, CCRP    703-208-6606    kelly.jeffords@inova.org   
Principal Investigator: Jennifer DeSimone, MD         
Sponsors and Collaborators
miRagen Therapeutics, Inc.
Investigators
Study Director: Paul Rubin, MD miRagen Therapeutics, Inc.
  More Information

Publications:
Olsen EA, Whittaker S, Kim YH, Duvic M, Prince HM, Lessin SR, Wood GS, Willemze R, Demierre MF, Pimpinelli N, Bernengo MG, Ortiz-Romero PL, Bagot M, Estrach T, Guitart J, Knobler R, Sanches JA, Iwatsuki K, Sugaya M, Dummer R, Pittelkow M, Hoppe R, Parker S, Geskin L, Pinter-Brown L, Girardi M, Burg G, Ranki A, Vermeer M, Horwitz S, Heald P, Rosen S, Cerroni L, Dreno B, Vonderheid EC; International Society for Cutaneous Lymphomas; United States Cutaneous Lymphoma Consortium; Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer. Clinical end points and response criteria in mycosis fungoides and Sézary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer. J Clin Oncol. 2011 Jun 20;29(18):2598-607. doi: 10.1200/JCO.2010.32.0630. Epub 2011 May 16.
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA; Alliance, Australasian Leukaemia and Lymphoma Group; Eastern Cooperative Oncology Group; European Mantle Cell Lymphoma Consortium; Italian Lymphoma Foundation; European Organisation for Research; Treatment of Cancer/Dutch Hemato-Oncology Group; Grupo Español de Médula Ósea; German High-Grade Lymphoma Study Group; German Hodgkin's Study Group; Japanese Lymphorra Study Group; Lymphoma Study Association; NCIC Clinical Trials Group; Nordic Lymphoma Study Group; Southwest Oncology Group; United Kingdom National Cancer Research Institute. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68.

Responsible Party: miRagen Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02580552     History of Changes
Other Study ID Numbers: MRG106-11-101
First Submitted: October 15, 2015
First Posted: October 20, 2015
Last Update Posted: November 8, 2017
Last Verified: November 2017

Keywords provided by miRagen Therapeutics, Inc.:
Cutaneous T-cell Lymphoma
CTCL
Mycosis Fungoides
Chronic lymphocytic leukemia
CLL
Diffuse large B-cell lymphoma
DLBCL
Adult T-cell leukemia/lymphoma
ATLL

Additional relevant MeSH terms:
Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoma, T-Cell
Lymphoma, Large B-Cell, Diffuse
Mycoses
Mycosis Fungoides
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Lymphoma, Non-Hodgkin