NCT04054245撤回2 期
Open Label Phase 2 Single Agent Study of PAT-1251 in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), or Post-Essential Thrombocytosis Myelofibrosis (Post-ET MF)
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Objective response rate (ORR)
研究概览
简要总结
This phase II trial studies how well PAT-1251 works in treating patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocytosis myelofibrosis. PAT-1251 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
详细描述
PRIMARY OBJECTIVES:
I. To determine the efficacy of LOXL2 inhibitor PAT-1251 (PAT-1251) as therapy for primary myelofibrosis (PMF), post-polycythemia vera (PV) myelofibrosis (MF), and post-essential thrombocytosis (ET) MF.
II. To determine the objective response of PAT-1251 treatment which is defined as CR (complete remission) + PR (partial remission) + CI (clinical improvement) after three and six cycles of treatment.
SECONDARY OBJECTIVES:
I. To determine the safety of PAT-1251 as therapy for PMF, post-PV MF and post-ET MF.
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 provide written informed consent
- •Willing and able to comply with scheduled visits, treatment plan and laboratory tests
- •Patient is able to swallow and retain oral medication
- •Must be diagnosed with treatment requiring PMF or post ET/PV MF with intermediate -1, intermediate -2 or high risk disease according to the International Working Group (IWG) prognostic scoring system, or if with low risk disease then with symptomatic splenomegaly that is greater than or equal to 5 cm below left costal margin by physical exam
- •Patients who are not candidates for, intolerant of, or relapsed/refractory to ruxolitinib
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (1500/mm^3)
- •Serum direct bilirubin =< 2.0 x ULN (upper limit of normal)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) (if both measured, then this applies to both measurements) =< 2.5 x ULN, except for patients with MF involvement of the liver who must have levels =< 5 x ULN
- •Treatment-related toxicities from prior therapies must have resolved to grade =< 1
- •At least 2 weeks from prior MF-directed treatment (till the start of study drug)
排除标准
- •Any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while in the study or that could confound discrimination between disease- and study treatment-related toxicities
- •Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
- •History or presence of ventricular tachyarrhythmia
- •Presence of unstable atrial fibrillation (ventricular response > 100 beats per minute [bpm]); patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria
- •Clinically significant resting bradycardia (< 50 bpm)
- •Angina pectoris or acute myocardial infarction =< 3 months prior to starting study drug
- •Other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
- •Patients who are currently receiving chronic (> 14 days) treatment with corticosteroids at a dose >= 10 mg of prednisone (or its glucocorticoid equivalent) per day, or any other chronic immunosuppressive treatment that cannot be discontinued prior to starting study drug
- •Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PAT-1251 as per physicians opinion
- •Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive - human chorionic gonadotropin (HCG) laboratory test
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 90 days after study treatment. Highly effective contraception methods include:
- •Total abstinence or
- •Male partner or female sterilization or
- •Combination of any two of the following (a+b or a+c, or b+c):
- •Use of oral, injected or implanted hormonal methods of contraception
- •Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- •Barrier methods of contraception: condom for male partner or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
- •Note: Postmenopausal women are allowed to participate in this study. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of asomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, a woman is considered to be of not child bearing potential only when her reproductive status has been confirmed by follow-up hormone level assessment
- •Sexually active males must use a condom during intercourse while taking the drug and for 3 months after stopping study drug and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
研究组 & 干预措施
Treatment (LOXL2 inhibitor PAT-1251)
Experimental
Patients receive LOXL2 inhibitor PAT-1251 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: LOXL2 Inhibitor PAT-1251 (Drug)
Treatment (LOXL2 inhibitor PAT-1251)
Experimental
Patients receive LOXL2 inhibitor PAT-1251 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Quality-of-Life Assessment (Other)
Treatment (LOXL2 inhibitor PAT-1251)
Experimental
Patients receive LOXL2 inhibitor PAT-1251 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Questionnaire Administration (Other)
结局指标
主要结局
Objective response rate (ORR)
时间窗: Up to 6 cycles, each cycle is 28 days.
Will be defined as complete remission (CR) + partial remission (PR) + clinical improvement (CI). Responses will be categorized according to the revised International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN) consensus criteria for myelofibrosis. Will be estimated along with the exact 95% confidence interval.
次要结局
- The Descriptive statistics in Improvements of transfusion dependence.(Baseline up to 2 years)
- Duration of response(From the date at which the patient's objective status is first noted to be a CR, PR, or CI to the date of progression (no longer meeting criteria for either CR, PR, or CI) is documented (if one has occurred), assessed up to 2 years)
- The Transfusion of independent patients(Baseline up to 2 years)
- Incidence of adverse events (AEs)(Up to 2 years)
- Changes in symptom burden(Baseline up to 2 years)
- The Descriptive statistics in the improvement of anemia(Baseline up to 2 years)
- Time to response(From date of first treatment to the first date at which the subject's objective status was classified as a response (CR, PR, or CI), assessed up to 2 years)
- Proportion of transfusion dependent patients who become transfusion independent and have a 1 g/dL increase in hemoglobin(Baseline up to 2 years)
- Proportion of transfusion dependent patients who become transfusion independent(Baseline up to 2 years)
- Proportion of transfusion independent patients requiring a transfusion(Baseline up to 2 years)
研究者
研究点 (1)
Loading locations...
相似试验
终止
2 期
P1101 in Treating Patients With MyelofibrosisPrimary MyelofibrosisSecondary MyelofibrosisNCT02370329Mayo Clinic11
进行中（未招募）
2 期
Study of Canakinumab in Patients With MyelofibrosisPost-essential Thrombocythemia MyelofibrosisET-MFPost-polycythemia Vera Related MyelofibrosisPV-MFPrimary MyelofibrosisNCT05467800John Mascarenhas14
已完成
2 期
An Investigational Drug, PF-02341066, Is Being Studied In Patients With Advanced Non-Small Cell Lung Cancer With A Specific Gene Profile Involving The Anaplastic Lymphoma Kinase (ALK) GeneCarcinoma, Non-Small-Cell LungNCT00932451Pfizer1,069
已完成
1 期
A Study of FT-2102 in Patients With Advanced Solid Tumors and Gliomas With an IDH1 MutationCohort 1a and 1b: Glioma (Advanced Gliomas and Glioblastoma Multiforme)Cohort 2a and 2b: Hepatobiliary Tumors (Hepatocellular Carcinoma, Bile Duct Carcinoma, Intrahepatic Cholangiocarcinoma, Other Hepatobiliary Carcinomas)Cohort 3a and 3b: ChondrosarcomaCohort 4a and 4b: Intrahepatic CholangiocarcinomaCohort 5a: Other Non-Central Nervous System Solid Tumors With IDH1 MutationsNCT03684811Forma Therapeutics, Inc.93
撤回
1 期
A Study of APG-1252 in Patients With Myelofibrosis Who Progressed After Initial TherapyMyelofibrosisNCT04354727Ascentage Pharma Group Inc.