An Open-Label, Multi-Center Phase 2 Clinical Trial Evaluating SNS-301 in Patients With ASPH+ High Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Minimal residual disease by IWG 2006 criteria
研究概览
简要总结
To evaluate safety, immunogenicity and anti-tumor responses of intradermally delivered SNS-301 in patients with ASPH+ high risk MDS and CMML.
详细描述
This phase 2, open-label, multi-center trial to evaluate the safety, immunogenicity and preliminary clinical efficacy of intradermally-delivered SNS-301 delivered using the 3M® hollow microstructured transdermal system (hMTS) device in patients with ASPH+ high risk myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML). The trial population consists of high risk ≥ Intermediate Risk-3 (IR-3) MDS and CMML-2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Signed informed consent.
- •Be 18 years of age or older.
- •Confirmed diagnosis of MDS or CMML.
- •Assessment of high-risk-MDS/CMML status defined as follows:
- •MDS: IPSS-R criteria for categorization ≥ Intermediate Risk-3
- •CMML: WHO criteria for CMML-2 (peripheral blasts of 5% to 19%, and 10% to 19% bone marrow blasts and/or presence of Auer rods).
- •Be willing to provide a fresh bone marrow aspirate sample at pre-treatment and demonstrate ASPH expression by flow cytometry.
- •Patient who has relapsed or is refractory / intolerant of hypomethylating agents (HMAs) or not responding to 4 treatment cycles of decitabine or 6 treatment cycles of azacytidine or progressing at any point after initiation of an HMA.
- •Patient refuses or is not considered a candidate for intensive induction chemotherapy using consensus criteria for defining such patients.
- •Patients with CMML must have been treated with at least 1 prior therapy (hydroxyurea or an HMA).
- •Eastern Cooperative Oncology Group (ECOG) Performance Scale 0-
- •Demonstrate adequate organ function: renal, hepatic, coagulation parameters.
- •For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use two highly effective contraceptive methods during the treatment period and for at least 180 days after the last dose of study treatment. For male patients: Agree that during the period specified above, men will not father a child. Male patients must remain abstinent, must be surgically sterile during the treatment period and for at least 180 days after the last dose of study treatment.
排除标准
- •Any approved anti-cancer therapy including chemotherapy, targeted small molecule therapy or radiation therapy within 2 weeks prior to trial Day
- •Participated on a clinical trial of an investigational agent and/or investigational device within 28 days prior to Day
- •Malignancies other than indications open for enrollment within 3 years prior to Day
- •Diagnosis of a core binding factor leukemia (t(8;21), t(16;16); or inv(16)) or diagnosis of acute promyelocytic leukemia (t(15;17)).
- •Active or history of autoimmune disease or immune deficiency.
- •History of HIV. HIV antibody testing recommended per investigator's clinical suspicion.
- •Active hepatitis B (hepatitis B surface antigen reactive) or active hepatitis C (HCV qualitative RNA detected); testing recommended per investigator's clinical suspicion.
- •Severe infections within 4 weeks prior to enrollment.
- •Received therapeutic oral or IV antibiotics within 2 weeks prior to Day
- •History or current evidence of any condition, therapy or laboratory abnormality that in the opinion of the treating investigator might confound the results of the trial.
- •Known previous or ongoing, active psychiatric or substance abuse disorders that would interfere with the requirements of the trial.
- •Treatment with systemic immunomodulating agents (including but not limited to IFNs, IL-2) within 6 weeks or five half-lives of the drug, whichever is shorter, prior to first dose.
- •Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study.
研究组 & 干预措施
SNS-301
SNS-301
干预措施: SNS-301 (Drug)
结局指标
主要结局
Minimal residual disease by IWG 2006 criteria
时间窗: 12 weeks
Minimal residual disease by peripheral and bone marrow blast count during the study
Adverse events of SNS-301
时间窗: 12 weeks
Number of adverse events including adverse events of special interest as assessed by CTCAE v5.0
Objective response rate by International Working Group (IWG) 2006 criteria
时间窗: 12 weeks
Best objective response during the study
Duration of Response by IWG 2006 criteria
时间窗: 12 weeks
Duration of response calculated from date of first response to date of progression
Overall Survival
时间窗: 36 months
Overall survival calculated from date of treatment to date of death
Disease control rate (DCR) by IWG 2006 criteria
时间窗: 12 weeks
Disease control rate calculated as the proportion of patients with stable disease or better
Progression Free Survival (PFS) as assessed by IWG 2006 criteria
时间窗: 12 weeks
Progression free survival calculated from the date of start of treatment to date of progression
次要结局
- Measurement of ASPH specific responses(up to 12 weeks)
- Measurement of T cell immune response(up 12 weeks)
- Measurement B cell immune responses(up to 12 weeks)
- Evaluation of immune gene transcript profiles(up to12 weeks)
- Measurement of pro-inflammatory and/or immunosuppressive molecules(up to 12 weeks)
- Measurement of oncoprotein expression(up to 12 weeks)