AzTrials
AzTrials

Cutaneous T-cell Lymphoma (CTCL)Phase 1NCT02580552

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

A Phase 1 study testing Cobomarsen in people with Cutaneous T-cell Lymphoma (CTCL) and Mycosis Fungoides (MF), run by miRagen Therapeutics, Inc. at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cobomarsen
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
19 sitesUnited States
Study dates
9 Feb 2016to 6 Oct 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

  • University of Colorado, Anschutz Medical Campus

    Aurora, Colorado, 80045

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Northwestern University; Department of Dermatology

    Chicago, Illinois, 60611

  • The Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • City of Hope

    Duarte, California, 91010

  • Inova Melanoma and Skin Cancer Center / Inova Schar Cancer Institute

    Fairfax, Virginia, 22003

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

  • UCSD Moores Cancer Center

    La Jolla, California, 92093

  • UCLA Department of Medicine

    Los Angeles, California, 90095

  • University of Miami Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Smilow Cancer Hospital at Yale-New Haven

    New Haven, Connecticut, 06510

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Weill Cornell Medicine

    New York, New York, 10065

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Chao Family Comprehensive Cancer Center at University of California, Irvine

    Orange, California, 92868

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • Stanford University Hospital and Clinics

    Stanford, California, 94063

  • Montefiore Medical Center, Albert Einstein College of Medicine

    The Bronx, New York, 10467

Other trials in United States

About this study

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

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.

Read the 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.
Being tested
Cobomarsen
Keywords
Cutaneous T-cell Lymphoma, CTCL, Mycosis Fungoides, Chronic lymphocytic leukemia, CLL, Diffuse large B-cell lymphoma, DLBCL, Adult T-cell leukemia/lymphoma, ATLL
Medical subject headings
Lymphoma, T-Cell, Cutaneous, Mycosis Fungoides, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Leukemia-Lymphoma, Adult T-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CobomarsenDrug

    Also called MRG-106

Study groups in NCT02580552
Study groupRoleWhat they receive
Part A, MFExperimentalIntratumoral Injection of cobomarsen
Receives: Drug: Cobomarsen
Part B, MFExperimentalSubcutaneous, intravenous or a combination of systemic and intratumoral administration of cobomarsen with or without stable background therapy
Receives: Drug: Cobomarsen
Part C, MFExperimentalSubcutaneous or intravenous administration of cobomarsen as monotherapy
Receives: Drug: Cobomarsen
Part D, CLLExperimentalSubcutaneous or intravenous administration of cobomarsen as monotherapy
Receives: Drug: Cobomarsen
Part E, DLBCL, activated B-cell (ABC) subtypeExperimentalSubcutaneous or intravenous administration of cobomarsen as monotherapy
Receives: Drug: Cobomarsen
Part F, ATLLExperimentalSubcutaneous or intravenous administration of cobomarsen as monotherapy
Receives: Drug: Cobomarsen

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability of cobomarsen based on vital signs, physical examination, clinical laboratory tests, ECG, and incidence and severity of adverse events

    Measured: From start of treatment to end of study participation

Secondary outcomes (14)

  1. Area under the plasma concentration vs. time curve (AUC) of cobomarsen following single and repeat doses administered intratumorally, subcutaneously or intravenously

    Measured: Up to 56 days

  2. Peak plasma concentration (Cmax) of cobomarsen following single and repeat doses administered intratumorally, subcutaneously or intravenously

    Measured: Up to 56 days

  3. Trough plasma concentration (Ctrough) of cobomarsen following each 4-week cycle of dosing

    Measured: Monthly from Week 5 up to end of study participation

  4. Skin disease severity (index lesions) - MF only

    Changes in MF skin lesion severity before and after treatment based on the Composite Assessment of Index Lesion Severity (CAILS) score

    Measured: Every 2 weeks from start of treatment until end of study participation

  5. Skin disease severity (whole body) - MF only

    Changes in MF skin lesion severity before and after treatment based on the modified Severity Weighted Assessment Tool (mSWAT) score

    Measured: Every 2 weeks from start of treatment until end of study participation

  6. Overall Response Rate in the skin - MF

    Proportion of subjects who achieve a partial response (PR) or complete response (CR) in the skin, based on SWAT score

    Measured: Approximately 1 year

  7. Overall Response Rate - CLL

    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

    Measured: Approximately 1 year

  8. Minimal Residual Disease (MRD) - CLL only

    Proportion of subjects who achieve a CR with no evidence of MRD by flow cytometry

    Measured: Approximately 1 year

  9. Overall Response Rate - DLBCL

    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

    Measured: Approximately 1 year

  10. Overall Response Rate - ATLL

    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

    Measured: Approximately 1 year

  11. Duration of Response

    Number of days from initial date of confirmed PR or CR until loss of response or relapse

    Measured: Up to approximately 2 years

  12. Time to Progression

    Number of days from first dose until objective disease progression

    Measured: Up to approximately 2 years

  13. Progression Free Survival (PFS)

    Number of days from first dose until objective disease progression or death from any cause

    Measured: Up to approximately 2 years

  14. Overall Survival (OS)

    Number of days from first dose until death from any cause

    Measured: Up to approximately 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Oct 2015 (estimated)
  2. Study start9 Feb 2016
  3. Primary completion6 Oct 2020
  4. Study completion6 Oct 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02580552
Sponsor's protocol ID
MRG106-11-101
Status last verified
Nov 2020
First submitted
15 Oct 2015
Last updated
23 Nov 2020
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Publications

  • van Kester MS, Ballabio E, Benner MF, Chen XH, Saunders NJ, van der Fits L, van Doorn R, Vermeer MH, Willemze R, Tensen CP, Lawrie CH. miRNA expression profiling of mycosis fungoides. Mol Oncol. 2011 Jun;5(3):273-80. doi: 10.1016/j.molonc.2011.02.003. Epub 2011 Feb 24.

    PubMed 21406335

  • Moyal L, Barzilai A, Gorovitz B, Hirshberg A, Amariglio N, Jacob-Hirsch J, Maron L, Feinmesser M, Hodak E. miR-155 is involved in tumor progression of mycosis fungoides. Exp Dermatol. 2013 Jun;22(6):431-3. doi: 10.1111/exd.12161.

    PubMed 23711069

  • Maj J, Jankowska-Konsur A, Sadakierska-Chudy A, Noga L, Reich A. Altered microRNA expression in mycosis fungoides. Br J Dermatol. 2012 Feb;166(2):331-6. doi: 10.1111/j.1365-2133.2011.10669.x. Epub 2012 Jan 9.

    PubMed 21966986

  • Kopp KL, Ralfkiaer U, Gjerdrum LM, Helvad R, Pedersen IH, Litman T, Jonson L, Hagedorn PH, Krejsgaard T, Gniadecki R, Bonefeld CM, Skov L, Geisler C, Wasik MA, Ralfkiaer E, Odum N, Woetmann A. STAT5-mediated expression of oncogenic miR-155 in cutaneous T-cell lymphoma. Cell Cycle. 2013 Jun 15;12(12):1939-47. doi: 10.4161/cc.24987. Epub 2013 May 15.

    PubMed 23676217

  • Eis PS, Tam W, Sun L, Chadburn A, Li Z, Gomez MF, Lund E, Dahlberg JE. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3627-32. doi: 10.1073/pnas.0500613102. Epub 2005 Feb 28.

    PubMed 15738415

  • Cui B, Chen L, Zhang S, Mraz M, Fecteau JF, Yu J, Ghia EM, Zhang L, Bao L, Rassenti LZ, Messer K, Calin GA, Croce CM, Kipps TJ. MicroRNA-155 influences B-cell receptor signaling and associates with aggressive disease in chronic lymphocytic leukemia. Blood. 2014 Jul 24;124(4):546-54. doi: 10.1182/blood-2014-03-559690. Epub 2014 Jun 9.

    PubMed 24914134

  • Guinn D, Ruppert AS, Maddocks K, Jaglowski S, Gordon A, Lin TS, Larson R, Marcucci G, Hertlein E, Woyach J, Johnson AJ, Byrd JC. miR-155 expression is associated with chemoimmunotherapy outcome and is modulated by Bruton's tyrosine kinase inhibition with Ibrutinib. Leukemia. 2015 May;29(5):1210-3. doi: 10.1038/leu.2014.344. Epub 2014 Dec 9. No abstract available.

    PubMed 25486872

  • Tomita M. Important Roles of Cellular MicroRNA miR-155 in Leukemogenesis by Human T-Cell Leukemia Virus Type 1 Infection. ISRN Microbiol. 2012 Sep 18;2012:978607. doi: 10.5402/2012/978607. Print 2012.

    PubMed 23762762

  • 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 Sezary 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.

    PubMed 21576639

  • Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, Hillmen P, Keating MJ, Montserrat E, Rai KR, Kipps TJ; International Workshop on Chronic Lymphocytic Leukemia. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 2008 Jun 15;111(12):5446-56. doi: 10.1182/blood-2007-06-093906. Epub 2008 Jan 23.

    PubMed 18216293

  • 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 Espanol de Medula Osea; 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. doi: 10.1200/JCO.2013.54.8800.

    PubMed 25113753

  • Tsukasaki K, Hermine O, Bazarbachi A, Ratner L, Ramos JC, Harrington W Jr, O'Mahony D, Janik JE, Bittencourt AL, Taylor GP, Yamaguchi K, Utsunomiya A, Tobinai K, Watanabe T. Definition, prognostic factors, treatment, and response criteria of adult T-cell leukemia-lymphoma: a proposal from an international consensus meeting. J Clin Oncol. 2009 Jan 20;27(3):453-9. doi: 10.1200/JCO.2008.18.2428. Epub 2008 Dec 8.

    PubMed 19064971

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Cobomarsen in people with Cutaneous T-cell Lymphoma (CTCL) and Mycosis Fungoides (MF), run by miRagen Therapeutics, Inc. at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02580552, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2020.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in