A Phase II Study of CPX-351 as a Novel Therapeutic Approach for Patients With Myelodysplastic Syndromes (MDS) After Hypomethylating Agent Failure
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- Efficacy of CPX-351 as Measured by Overall Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of treatment with CPX-351 (an FDA approved drug for the treatment of AML) in individuals with MDS while using a new stratification tool to predict outcomes of participants following HMA failure. This approach is intended to gain a better understanding and insight into identifying new opportunities for drug approvals in this setting.
详细描述
This study will evaluate efficacy of treatment with CPX-351in participants with MDS while using a new stratification tool to predict outcomes of patients following HMA failure in order to gain a better understanding and insight into identifying new opportunities for drug approvals in this setting.
CPX-351is an investigational (experimental) drug for the indication of myelodysplastic syndrome that works by delivering two chemotherapy medications (daunorubicin and cytarabine) together which are then concentrated into the bone marrow (the part of the body that makes blood cells). CPX-351 is experimental because it is not approved by the Food and Drug Administration (FDA) for the indication of myelodysplastic syndrome. This drug is approved by theFDA for the indication of acute myeloid leukemia. One or more of the Investigators conducting this study serve as consultants for the company that makes products used in this study. These financial interests are within permissible limits established by the local institutional Conflict of Interest Policy.
Prior to beginning treatment, all eligible participants will be grouped into low risk versus high risk based on a stratification tool used to determine their disease. Group 1 will be low risk participants and group 2 will be high risk participants. All study participants will get the same study drug, CPX-351. Participants will receive the CPX-351 on days 1, 3 and 5 of the first 28 day cycle. After participants finish the first round of treatment and based on their response they may be eligible for another 4 cycles of treatment. The participant's doctor will inform them if this is an available option when the time comes. Once participant have finished treatment, their doctor will continue observe for side effects and follow their condition for 1 year.
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
- •Patients must give voluntary written consent before performance of any study related procedures not part of standard medical care
- •Diagnosis of MDS or MDS/MPN according to 2016 WHO criteria12
- •Primary therapy failure with either hypomethylating agents (decitabine or azacitidine) defined as:
- •Progression (according to 2006 IWG criteria)13 after initiation of azacitidine or decitabine treatment; or
- •Failure to achieve complete or partial response or hematological improvement (according to 2006 IWG)13 after at least 4-6 cycles (4-weeks cycle) of azacitidine or decitabine; or
- •Relapse after initial complete or partial response or hematological improvement (according to 2006 IWG criteria)13 observed after at least 4 cycles of azacitidine or decitabine.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status < 2
- •Subjects must have normal organ and marrow function defined as:
- •If total bilirubin < 2x upper limit of normal (</= 3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome) at the discretion of the treating physician following discussion with PI)
- •Calculated creatinine clearance value of > 30ml/min AND a serum creatinine < 1.5mg/dL
- •LVEF >/= 50%
- •Female patients who:
- •Are postmenopausal for at least 1 year before the screening visit, OR
- •Are surgically sterile, OR
- •Agree to practice true abstinence from heterosexual contact or agree to use effective contraception without interruption during the study therapy and 90 days after the last dose
- •Male patients who:
- •Are surgically sterile, OR
- •Agree to practice true abstinence from heterosexual contact or agree to use effective contraception without interruption during the study therapy and 90 days after the last dose
排除标准
- •Prior treatment with CPX-351, or known hypersensitivity to CPX-351 or its components.
- •Prior treatment with intensive chemotherapy.
- •Any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent.
- •Any active malignancy (unrelated, non-hematological malignancy) diagnosed within the past 6 months of starting the study drug (other than curatively treated carcinoma-in-situ of the cervix or non-melanoma skin cancer).
- •Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Known history of HIV or active hepatitis B or C.
- •Major surgery within 2 weeks prior to study enrollment.
- •Pregnant or lactating females
- •Male and female patients who are fertile who do not agree to use an effective barrier methods of birth control (i.e. abstinence or 2 forms of contraception) to avoid pregnancy while receiving study treatment.
研究组 & 干预措施
intravenous CPX-351 with potential maintenance therapy
Single agent CPX-351 administered at the standard FDA approved dose of 44 mg/m2 intravenously on days 1, 3, 5 of the induction cycle. If participants achieve complete remission (CR), complete remission with incomplete count recovery (CRi) or partial remission (PR), they will be eligible to continue on to maintenance therapy, which will consist of CPX351 at a dose of 15.4 mg/m2 every 28 days. Participants can receive up to 4 cycles of maintenance therapy.
干预措施: CPX-351 (Drug)
结局指标
主要结局
Efficacy of CPX-351 as Measured by Overall Response Rate (ORR)
时间窗: day 28 +/- 7 days of induction
Efficacy of CPX as measured by ORR as defined by IWG 2006 criteria for MDS participants at end of induction. IWG 2006 responses that must be for at least 4 weeks include Complete Remission (CR), Partial Remission (PR), Marrow CR, Stable Disease (SD), Failure, Relapse after CR or PR (PD), or cytogenetic response. Hematologic Improvement (HI), which must be for at least 8 weeks, includes erythroid response (pretreatment, \< 11 g/dL), Platelet response (pretreatment, \< 100x109/L), Neutrophil response (pretreatment, \< 1 x109/L), or Progression or relapse after HI.
次要结局
- Time to Response (TTR) Associated With CPX-351(day 28 +/- 7 days of induction)
- Duration of Response (DOR) in Participants Achieving a Response(up to 1 year after end of treatment)
- Overall Survival (OS)(up to 1 year after end of treatment)
- Event-free Survival (EFS)(up to 1 year after end of treatment)
研究者
Sudipto Mukherjee
Principal Investigator
Case Comprehensive Cancer Center