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

NCT ID: NCT02580552

Last Updated: 2020-11-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

66 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-09

Study Completion Date

2020-10-06

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Cutaneous T-cell Lymphoma (CTCL) Mycosis Fungoides (MF) Chronic Lymphocytic Leukemia (CLL) Diffuse Large B-Cell Lymphoma (DLBCL), ABC Subtype Adult T-Cell Leukemia/Lymphoma (ATLL)

Keywords

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Cutaneous T-cell Lymphoma CTCL Mycosis Fungoides Chronic lymphocytic leukemia CLL Diffuse large B-cell lymphoma DLBCL Adult T-cell leukemia/lymphoma ATLL

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part A, MF

Intratumoral Injection of cobomarsen

Group Type EXPERIMENTAL

Cobomarsen

Intervention Type DRUG

Part B, MF

Subcutaneous, intravenous or a combination of systemic and intratumoral administration of cobomarsen with or without stable background therapy

Group Type EXPERIMENTAL

Cobomarsen

Intervention Type DRUG

Part C, MF

Subcutaneous or intravenous administration of cobomarsen as monotherapy

Group Type EXPERIMENTAL

Cobomarsen

Intervention Type DRUG

Part D, CLL

Subcutaneous or intravenous administration of cobomarsen as monotherapy

Group Type EXPERIMENTAL

Cobomarsen

Intervention Type DRUG

Part E, DLBCL, activated B-cell (ABC) subtype

Subcutaneous or intravenous administration of cobomarsen as monotherapy

Group Type EXPERIMENTAL

Cobomarsen

Intervention Type DRUG

Part F, ATLL

Subcutaneous or intravenous administration of cobomarsen as monotherapy

Group Type EXPERIMENTAL

Cobomarsen

Intervention Type DRUG

Interventions

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Cobomarsen

Intervention Type DRUG

Other Intervention Names

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MRG-106

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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miRagen Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Diana M. Escolar, MD, FAAN

Role: STUDY_DIRECTOR

miRagen Therapeutics, Inc.

Locations

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City of Hope

Duarte, California, United States

Site Status

UCSD Moores Cancer Center

La Jolla, California, United States

Site Status

UCLA Department of Medicine

Los Angeles, California, United States

Site Status

Chao Family Comprehensive Cancer Center at University of California, Irvine

Orange, California, United States

Site Status

Stanford University Hospital and Clinics

Stanford, California, United States

Site Status

University of Colorado, Anschutz Medical Campus

Aurora, Colorado, United States

Site Status

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, United States

Site Status

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, United States

Site Status

Northwestern University; Department of Dermatology

Chicago, Illinois, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

University of Nebraska Medical Center

Omaha, Nebraska, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Weill Cornell Medicine

New York, New York, United States

Site Status

Montefiore Medical Center, Albert Einstein College of Medicine

The Bronx, New York, United States

Site Status

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Inova Melanoma and Skin Cancer Center / Inova Schar Cancer Institute

Fairfax, Virginia, United States

Site Status

Countries

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United States

References

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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.

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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.

Reference Type BACKGROUND
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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.

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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.

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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.

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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.

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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.

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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.

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Other Identifiers

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MRG106-11-101

Identifier Type: -

Identifier Source: org_study_id