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.
Brief Title
Safety, Tolerability and Pharmacokinetics of MRG-106 in Patients With Mycosis Fungoides (MF), CLL, DLBCL or ATLL
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.
* 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.
Completion Date
Completion Date Type
Actual
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)
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
* 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
Inclusion 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.
* 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.
Gender
All
Gender Based
false
Keywords
Cutaneous T-cell Lymphoma
CTCL
Mycosis Fungoides
Chronic lymphocytic leukemia
CLL
Diffuse large B-cell lymphoma
DLBCL
Adult T-cell leukemia/lymphoma
ATLL
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02580552
Org Class
Industry
Org Full Name
miRagen Therapeutics, Inc.
Org Study Id
MRG106-11-101
Overall Status
Completed
Phases
Phase 1
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Measure
Safety and tolerability of cobomarsen based on vital signs, physical examination, clinical laboratory tests, ECG, and incidence and severity of adverse events
Outcome Time Frame
From start of treatment to end of study participation
Secondary Outcomes
Outcome Time Frame
Up to 56 days
Outcome Measure
Area under the plasma concentration vs. time curve (AUC) of cobomarsen following single and repeat doses administered intratumorally, subcutaneously or intravenously
Outcome Time Frame
Up to 56 days
Outcome Measure
Peak plasma concentration (Cmax) of cobomarsen following single and repeat doses administered intratumorally, subcutaneously or intravenously
Outcome Time Frame
Monthly from Week 5 up to end of study participation
Outcome Measure
Trough plasma concentration (Ctrough) of cobomarsen following each 4-week cycle of dosing
Outcome Description
Changes in MF skin lesion severity before and after treatment based on the Composite Assessment of Index Lesion Severity (CAILS) score
Outcome Time Frame
Every 2 weeks from start of treatment until end of study participation
Outcome Measure
Skin disease severity (index lesions) - MF only
Outcome Description
Changes in MF skin lesion severity before and after treatment based on the modified Severity Weighted Assessment Tool (mSWAT) score
Outcome Time Frame
Every 2 weeks from start of treatment until end of study participation
Outcome Measure
Skin disease severity (whole body) - MF only
Outcome Description
Proportion of subjects who achieve a partial response (PR) or complete response (CR) in the skin, based on SWAT score
Outcome Time Frame
Approximately 1 year
Outcome Measure
Overall Response Rate in the skin - MF
Outcome 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
Outcome Time Frame
Approximately 1 year
Outcome Measure
Overall Response Rate - CLL
Outcome Description
Proportion of subjects who achieve a CR with no evidence of MRD by flow cytometry
Outcome Time Frame
Approximately 1 year
Outcome Measure
Minimal Residual Disease (MRD) - CLL only
Outcome 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
Outcome Time Frame
Approximately 1 year
Outcome Measure
Overall Response Rate - DLBCL
Outcome Description
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
Outcome Time Frame
Approximately 1 year
Outcome Measure
Overall Response Rate - ATLL
Outcome Description
Number of days from initial date of confirmed PR or CR until loss of response or relapse
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Duration of Response
Outcome Description
Number of days from first dose until objective disease progression
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Time to Progression
Outcome Description
Number of days from first dose until objective disease progression or death from any cause
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Progression Free Survival (PFS)
Outcome Description
Number of days from first dose until death from any cause
Outcome Time Frame
Up to approximately 2 years
Outcome Measure
Overall Survival (OS)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Noah Kornblum
Investigator Email
nkornblu@montefiore.org
Investigator Phone
718-920-4826
Categories Mesh Debug
Blood & Bone Marrow Cancers --- LEUKEMIA, LYMPHOCYTIC, CHRONIC, B-CELL
Cancer --- NEOPLASMS
Blood & Bone Marrow Cancers --- LYMPHOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- LYMPHATIC DISEASES
Blood & Bone Marrow Cancers --- IMMUNOPROLIFERATIVE DISORDERS
Infectious Disease --- IMMUNE SYSTEM DISEASES
Lung --- IMMUNE SYSTEM DISEASES
Blood & Bone Marrow Cancers --- LEUKEMIA, LYMPHOID
Cancer --- LEUKEMIA
Blood & Bone Marrow Cancers --- LEUKEMIA
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA
MeSH Terms
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
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
COBOMARSEN