NCT01928537已完成3 期
Phase IIIB, Open-label, Multi-Center Study of the Efficacy and Safety of Rigosertib Administered as 72-hour Continuous Intravenous Infusions in Patients With Myelodysplastic Syndrome With Excess Blasts Progressing On or After Azacitidine or Decitabine
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 35
- 主要终点
- Relationship of bone marrow blast response and overall survival.
研究概览
简要总结
This study will examine the effect intravenously administered rigosertib has on the relationship between bone marrow blasts response and overall survival in myelodysplastic syndromes (MDS) patients who have 5-30% bone marrow blasts and who progressed on or after treatment with azacitidine or decitabine.
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
- •Diagnosis of MDS confirmed within 6 weeks prior to Screening according to WHO criteria or French-American-British (FAB) classification.
- •MDS classified as follows, according to WHO criteria and FAB classification:
- •RAEB-1 (5% to 9% BM blasts)
- •RAEB-2 (10% to 19% BM blasts)
- •CMML (10% to 20% BM blasts) and white blood cells (WBC) < 13,000/μL
- •RAEB-t (20% to 30% BM blasts), meeting the following criteria: WBC < 25,000/μL at study entry; or, Stable White Blood Cell (WBC) at least 4 weeks prior to Screening and not requiring intervention for WBC control with hydroxyurea, chemotherapy, or leukopheresis.
- •At least one cytopenia (Absolute Neutrophil Count (ANC) < 1800/μL or Platelet (PLT) count < 100,000/μL or hemoglobin (Hgb) < 10 g/dL).
- •Progression (according to 2006 IWG criteria) at any time after initiation of subcutaneous or intravenous azacitidine or decitabine treatment per labeling during the past 2 years, defined as follows:
- •For patients with ˂ 5% BMBL, ≥ 50% increase in BMBL to ˃ 5% BMBL
- •For patients with 5-10% BMBL, ≥ 50% increase in BMBL to ˃ 10% BMBL
- •For patients with 10-20% BMBL, ≥ 50% increase in BMBL to ˃ 20% BMBL
- •For patients with 20-30% BMBL, ≥ 50% increase in BMBL to ˃ 30% BMBL
- •Any of the following: ≥ 50% decrease from maximum remission/response levels in granulocytes or PLT; Decrease in Hgb concentration by ≥ 2 g/dL; or, Transfusion dependence, defined as administration of at least 4 RBC units in the past 8 weeks before Screening (patients must have Hgb values ˂ 9 g/dL prior to transfusion to be considered), in the absence of another explanation.
- •Has failed to respond to, relapsed following, not eligible, or opted not to participate in bone marrow transplantation.
- •Off all other treatments for MDS for at least 4 weeks, except for azacitidine or decitabine. Filgrastim (G-CSF) and erythropoietin are allowed before and during the study as clinically indicated.
- •No medical need for induction chemotherapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or
- •Willing to adhere to the prohibitions and restrictions specified in this protocol.
- •Patient must signed an informed consent form.
排除标准
- •Previous participation in a clinical study of IV or oral rigosertib.
- •Anemia due to factors other than MDS (including hemolysis or gastrointestinal [GI] bleeding) unless stabilized for 1 week after RBC transfusion.
- •Any active malignancy within the past year, except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast.
- •Uncontrolled intercurrent illness including.
- •Active infection not adequately responding to appropriate therapy.
- •Total bilirubin ≥ 1.5 mg/dL not related to hemolysis or Gilbert's disease.
- •ALT/AST ≥ 2.5 x upper limit of normal (ULN).
- •Serum creatinine ≥ 2.0 mg/dL.
- •Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <130 mEq/L).
- •Female patients who are pregnant or lactating.
- •Patients who are unwilling to follow strict contraception requirements.
- •Female patients with reproductive potential who do not have a negative urine beta-human chorionic gonadotropin (βHCG) pregnancy test at Screening.
- •Major surgery without full recovery or major surgery within 3 weeks of Baseline/Cycle 1 Day 1 visit.
- •Uncontrolled hypertension (defined as a systolic pressure ≥160 mmHg and/or a diastolic pressure ≥ 110 mmHg).
- •New onset seizures (within 3 months prior to Baseline) or poorly controlled seizures.
- •Any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy.
- •Prior treatment with low-dose cytarabine during the past 2 years.
- •Investigational therapy within 4 weeks of Baseline/Day 1 visit.
- •Psychiatric illness or social situation that would limit the patient's ability to tolerate and/or comply with study requirements.
研究组 & 干预措施
rigosertib sodium
Experimental
Rigosertib sodium will be administered as a 72-hr continuous intravenous infusion consisting of 3 consecutive doses of 1800 mg over 24 hours on Days 1, 2, and 3 of a 14-day cycle for the first 8 cycles and then on Days 1, 2, and 3 of a 28-day cycle for the following cycles.
干预措施: rigosertib sodium (Drug)
结局指标
主要结局
Relationship of bone marrow blast response and overall survival.
时间窗: Up to 2 years.
Bone marrow blast response is defined as bone marrow (BM) complete response, ≥ 50% BM blast decrease from pretreatment value, or stable BM response (no progression) according to the International Working Group (IWG) 2006 criteria and overall survival. Overall survival is defined as the time from first study treatment to death from any cause. All patients will be followed until death and/or progression, even if they have discontinued treatment for whatever cause. Survival time of patients lost to follow-up will be censored at the time they were last known to be alive.
次要结局
- Progression-free survival.(Up to 2 years after study enrollment.)
- Number of patients with overall hematologic response.(Up to 2 years after study enrollment.)
- Number of patients with hematological improvement.(Up to 2 years after study enrollment.)
- Number of patients with cytogenetic response.(Up to 2 years after study enrollment.)
- Quality of Life Questionnaire(Up to 2 years after study enrollment.)
- Infections.(Up to 2 years after study enrollment.)
- Concentration of rigosertib in plasma.(Week 1 and week 3.)
- Safety.(Study enrollment until 30 days after patient's last dose of rigosertib up to 2 years.)
- Number of patients who transition to Acute Myeloid Leukemia (AML)(Up to 2 years after study enrollment.)
研究者
研究点 (35)
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