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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 19
- 主要终点
- Safety and tolerability of cobomarsen based on vital signs, physical examination, clinical laboratory tests, ECG, and incidence and severity of adverse events
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
Part B, MF
Subcutaneous, intravenous or a combination of systemic and intratumoral administration of cobomarsen with or without stable background therapy
干预措施: Cobomarsen (Drug)
Part A, MF
Intratumoral Injection of cobomarsen
干预措施: Cobomarsen (Drug)
Part C, MF
Subcutaneous or intravenous administration of cobomarsen as monotherapy
干预措施: Cobomarsen (Drug)
Part D, CLL
Subcutaneous or intravenous administration of cobomarsen as monotherapy
干预措施: Cobomarsen (Drug)
Part E, DLBCL, activated B-cell (ABC) subtype
Subcutaneous or intravenous administration of cobomarsen as monotherapy
干预措施: Cobomarsen (Drug)
Part F, ATLL
Subcutaneous or intravenous administration of cobomarsen as monotherapy
干预措施: Cobomarsen (Drug)
结局指标
主要结局
Safety and tolerability of cobomarsen based on vital signs, physical examination, clinical laboratory tests, ECG, and incidence and severity of adverse events
时间窗: From start of treatment to end of study participation
次要结局
- Overall Response Rate - CLL(Approximately 1 year)
- 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)
- Overall Response Rate in the skin - MF(Approximately 1 year)
- Minimal Residual Disease (MRD) - CLL only(Approximately 1 year)
- Overall Response Rate - ATLL(Approximately 1 year)
- Duration of Response(Up to approximately 2 years)
- Progression Free Survival (PFS)(Up to approximately 2 years)
- Overall Survival (OS)(Up to approximately 2 years)
- Time to Progression(Up to approximately 2 years)
- 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)
- Overall Response Rate - DLBCL(Approximately 1 year)