Phase 1 Study to Assess Tolerability, PK and PD Activity of ON 01910.Na Administered Orally as Escalating Single and Multiple Doses Twice a Day up to 14 Days of a 21-Day Cycle in Patients With Myelodysplastic Syndrome
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Hematologic and non-hematologic toxicities and the maximum tolerated dose (MTD) of orally administered ON 01910.Na given twice a day up to 14 days at doses escalating from 70 mg to 700 mg
研究概览
简要总结
In other clinical studies, ON 01910.Na has been safely given intravenously to Patients with advanced cancers. However, to treat some Patients, it may be better if ON 01910.Na could be given by mouth. This study will determine if it is safe to give ON 01910.Na by mouth, what is the highest dose can be safely given by mouth, and how much of the drug gets from the stomach into the blood stream when it is given by mouth.
详细描述
This is a three-part phase 1 study in which nineteen to one hundred two patients with Low, Intermediate-1, Intermediate-2, or High risk MDS will receive oral doses of ON 01910.Na Concentrate as escalating single or multiple doses (70mg to 700 mg bid) up to 14 days of a 21-day cycle.
Part I: Bioavailability and Tolerability of Single Oral Dosing (n=3):
In Part I of this trial the bioavailability and tolerability of oral ON1910.Na administered as single, oral, escalating doses in a fasting state (defined as no less than 30 minutes before next meal) will be determined in three patients with Low, Intermediate-1, Intermediate-2 or High Risk MDS. All three patients will receive during the first week a 70mg single oral dose and blood samples for pharmacokinetic analyses will be taken after dosing. In the absence of drug-related grade 2 toxicity or higher, single dosing will be escalated in each patient weekly to 140mg (week 2), 280mg (week 3), 560mg (week 4) and 700mg (week 5).
At the end of Part I (week 6), all patients will be eligible to be enrolled in Part II.
Part II: Determination of MTD (n=10-84):
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
- •≥ 18 years of age
- •Diagnosis of MDS confirmed within 6 weeks prior to study entry according to the World Health Organization (WHO) Criteria (see Attachment 1) or the French-American-British (FAB) Classification (see Attachment 2).
- •Low, Intermediate 1 or 2 or High Risk MDS according to the IPSS score (see Attachment 3)
- •At least one cytopenia (Absolute Neutrophil Count < 1500/µL or Platelet Count <100,000/µL or Hemoglobin <10 g/dL)
- •Failure of, or insufficient response to Azacytidine or Decitabine or Lenalidomide or to Erythrocyte Stimulating Agent
- •Failed to respond to, relapsed following, or opted not to participate in bone marrow transplantation
- •Off all other treatments for MDS (including filgrastim (G-CSF) and erythropoietin) for at least four weeks (only 2 weeks if PROCRITTM is used). Filgrastim (G-CSF) can be used before, during and after the protocol treatment for patients with documented febrile neutropenia (<500/µl)
- •ECOG Performance Status 0, 1 or 2 (see Attachment 4)
- •Willing to adhere to the prohibitions and restrictions specified in this protocol
- •Patient (or his/her legally authorized representative) must have signed an informed consent document indicating that he/she understands the purpose of and procedures required for the study and is willing to participate in the study
排除标准
- •Anemia due to factors other than MDS (including hemolysis or gastrointestinal bleeding)
- •Hypoplastic MDS (cellularity <10%)
- •Any active malignancy within the past year except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or breast
- •History of HIV-1 seropositivity
- •Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia
- •Active infection not adequately responding to appropriate therapy.
- •Total bilirubin > 1.5 mg/dL not related to hemolysis or Gilbert's disease, AST/ALT > 2 X ULN
- •Serum creatinine > 1.5 x ULN
- •Ascites requiring active medical management including paracentesis, or hyponatremia (defined as serum sodium value of <130 Meq/L).
- •Women patients who are pregnant or lactating; Male patients with female sexual partners who are unwilling to follow the strict contraception requirements described in this protocol (see Section 4.4).; Patients who do not agree to use adequate contraceptive [including prescription oral contraceptives (birth control pills), contraceptive injections, intrauterine device (IUD), double-barrier method (spermicidal jelly or foam with condoms or diaphragm), contraceptive patch, or surgical sterilization] before entry and throughout the study; Female patients with reproductive potential who do not have a negative serum or urine beta-HCG pregnancy test at screening
- •Major surgery without full recovery or major surgery within 3 weeks of ON 01910.Na treatment start.
- •Uncontrolled hypertension (defined as a systolic pressure ³ 160 mm Hg and/or a diastolic pressure ³ 110 mm Hg)
- •New onset seizures (within 3 months prior to the first dose of ON 01910.Na) or poorly controlled seizures
- •Any concurrent investigational agent or chemotherapy, radiotherapy or immunotherapy
- •Treatment with standard MDS therapies or investigational therapy within 4 weeks of starting ON 01910.Na
- •Psychiatric illness/social situations that would limit the patient's ability to tolerate and/or comply with study requirements
研究组 & 干预措施
ON 01910.Na
The maximum tolerated dose of oral ON 01910.Na administered in a fasting state (defined as no less than 30 min before next meal) twice a day for 14 days will be determined following an adaptive design at doses between 70 and 700mg.
干预措施: ON 01910.Na (Drug)
结局指标
主要结局
Hematologic and non-hematologic toxicities and the maximum tolerated dose (MTD) of orally administered ON 01910.Na given twice a day up to 14 days at doses escalating from 70 mg to 700 mg
时间窗: 2 years
次要结局
- Characterize pharmacokinetics in a fasting state of ON 01910.Na following administration by the oral route.(2 years)
- Determine any food effect on the pharmacokinetics and the absolute bioavailability of ON 01910.Na administered orally.(2 years)