Clinical Trials /

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

NCT02580552

Description:

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.

Related Conditions:
  • Adult T-Cell Leukemia/Lymphoma
  • Chronic Lymphocytic Leukemia
  • Diffuse Large B-Cell Lymphoma
  • Mycosis Fungoides
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: MRG106-11-101
  • NCT ID: NCT02580552

Conditions

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

Interventions

DrugSynonymsArms
CobomarsenMRG-106Part A, MF

Purpose

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

      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.
    

Trial Arms

NameTypeDescriptionInterventions
Part A, MFExperimentalIntratumoral Injection of cobomarsen
  • Cobomarsen
Part B, MFExperimentalSubcutaneous, intravenous or a combination of systemic and intratumoral administration of cobomarsen with stable background therapy
  • Cobomarsen
Part C, MFExperimentalSubcutaneous or intravenous administration of cobomarsen as monotherapy
  • Cobomarsen
Part D, CLLExperimentalSubcutaneous or intravenous administration of cobomarsen as monotherapy
  • Cobomarsen
Part E, DLBCL, activated B-cell (ABC) subtypeExperimentalSubcutaneous or intravenous administration of cobomarsen as monotherapy
  • Cobomarsen
Part F, ATLLExperimentalSubcutaneous or intravenous administration of cobomarsen as monotherapy
  • Cobomarsen

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure:Peak plasma concentration (Cmax) of cobomarsen following single and repeat doses administered intratumorally, subcutaneously or intravenously
Time Frame:Up to 56 days
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Skin disease severity (index lesions) - MF only
Time Frame:Every 2 weeks from start of treatment until end of study participation
Safety Issue:
Description:Changes in MF skin lesion severity before and after treatment based on the Composite Assessment of Index Lesion Severity (CAILS) score
Measure:Skin disease severity (whole body) - MF only
Time Frame:Every 2 weeks from start of treatment until end of study participation
Safety Issue:
Description:Changes in MF skin lesion severity before and after treatment based on the modified Severity Weighted Assessment Tool (mSWAT) score
Measure:Overall Response Rate - MF
Time Frame:Approximately 1 year
Safety Issue:
Description: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
Measure:Overall Response Rate - CLL
Time Frame:Approximately 1 year
Safety Issue:
Description: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
Measure:Minimal Residual Disease (MRD) - CLL only
Time Frame:Approximately 1 year
Safety Issue:
Description:Proportion of subjects who achieve a CR with no evidence of MRD by flow cytometry
Measure:Overall Response Rate - DLBCL
Time Frame:Approximately 1 year
Safety Issue:
Description: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
Measure:Overall Response Rate - ATLL
Time Frame:Approximately 1 year
Safety Issue:
Description: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
Measure:Duration of Response
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Number of days from initial date of confirmed PR or CR until loss of response or relapse
Measure:Time to Progression
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Number of days from first dose until objective disease progression
Measure:Progression Free Survival (PFS)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Number of days from first dose until objective disease progression or death from any cause
Measure:Overall Survival (OS)
Time Frame:Up to approximately 2 years
Safety Issue:
Description:Number of days from first dose until death from any cause

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:miRagen Therapeutics, Inc.

Trial Keywords

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

Last Updated

June 24, 2019