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

NCT02580552 | Completed Phase 1

• 1 other identifier: MRG106-11-101
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 19

Brief 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 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.

Conditions

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

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

Outcome Measures

Primary Outcomes (1)

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

  From start of treatment to end of study participation

Secondary Outcomes (14)

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

  Up to 56 days

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

  Up to 56 days

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

  Monthly from Week 5 up to end of study participation

• Skin disease severity (index lesions) - MF only

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

• Skin disease severity (whole body) - MF only

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

Other Outcomes (5)

• miR-155-5p expression in cutaneous lesions of subjects with MF

  At baseline and between Week 16 and end of study participation

• Proportion of neoplastic lymphoid cells in cutaneous lesions of subjects with MF

  At baseline and between Week 16 and end of study participation

• Proportions of immune cell subsets

  At baseline and monthly or bimonthly, up to end of study participation

Study Arms (6)

Part A, MF

EXPERIMENTAL

Intratumoral Injection of cobomarsen

Drug: Cobomarsen

Part B, MF

EXPERIMENTAL

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

Drug: Cobomarsen

Part C, MF

EXPERIMENTAL

Subcutaneous or intravenous administration of cobomarsen as monotherapy

Drug: Cobomarsen

Part D, CLL

EXPERIMENTAL

Subcutaneous or intravenous administration of cobomarsen as monotherapy

Drug: Cobomarsen

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

EXPERIMENTAL

Subcutaneous or intravenous administration of cobomarsen as monotherapy

Drug: Cobomarsen

Part F, ATLL

EXPERIMENTAL

Subcutaneous or intravenous administration of cobomarsen as monotherapy

Drug: Cobomarsen

Interventions

Cobomarsen DRUG

Also known as: MRG-106

Part A, MF; Part B, MF; Part C, MF; Part D, CLL; Part E, DLBCL, activated B-cell (ABC) subtype; Part F, ATLL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• miRagen Therapeutics, Inc.: lead

Study Sites (19)

City of Hope

Duarte, California, 91010, United States

Location

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

UCLA Department of Medicine

Los Angeles, California, 90095, United States

Location

Chao Family Comprehensive Cancer Center at University of California, Irvine

Orange, California, 92868, United States

Location

Stanford University Hospital and Clinics

Stanford, California, 94063, United States

Location

University of Colorado, Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

Smilow Cancer Hospital at Yale-New Haven

New Haven, Connecticut, 06510, United States

Location

University of Miami Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

Northwestern University; Department of Dermatology

Chicago, Illinois, 60611, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Montefiore Medical Center, Albert Einstein College of Medicine

The Bronx, New York, 10467, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Inova Melanoma and Skin Cancer Center / Inova Schar Cancer Institute

Fairfax, Virginia, 22003, United States

Location

Related Publications (12)

• 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.

  PMID: 21406335 BACKGROUND

• 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.

  PMID: 23711069 BACKGROUND

• 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.

  PMID: 21966986 BACKGROUND

• 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.

  PMID: 23676217 BACKGROUND

• 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.

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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.

  PMID: 24914134 BACKGROUND

• 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.

  PMID: 25486872 BACKGROUND

• 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.

  PMID: 23762762 BACKGROUND

• 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.

  PMID: 21576639 BACKGROUND

• 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.

  PMID: 18216293 BACKGROUND

• 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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MeSH Terms

Conditions

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

Interventions

cobomarsen

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, T-Cell

Study Officials

• Diana M. Escolar, MD, FAAN

  miRagen Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2015
• First Posted: October 20, 2015
• Study Start: February 9, 2016
• Primary Completion: October 6, 2020
• Study Completion: October 6, 2020
• Last Updated: November 23, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (19)