A Pilot Study of Ivosidenib for Patients With Clonal Cytopenia of Undetermined Significance and Mutations in IDH1
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 20
- 试验地点
- 3
- 主要终点
- Rate of improvement in hematologic parameters
研究概览
简要总结
This is an open-label, multicenter study exploring the efficacy of ivosidenib in patients with clonal cytopenia of undetermined significance (CCUS) with mutations in IDH1. The purpose is to establish proof of principle that ivosidenib is well-tolerated and potentially efficacious in improving blood count abnormalities in these patients.
The study will also be offered in a decentralized, remote structure to patients.
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
- •Unexplained cytopenia for at least 6 months. Cytopenia is defined as the presence of ≥1 blood count indexes below the following thresholds:
- •Hgb <10 g/dL
- •ANC <1.8 × 10^9/L
- •Platelets <100 × 10^9/L
- •IDH1 gene mutation (R132) confirmed by droplet digital PCR (ddPCR) testing, at a frequency > 2%. This will be performed locally and confirmed at Washington University.
- •At least 18 years of age.
- •ECOG performance status 0-2
- •Adequate organ function as defined below:
- •AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
- •Serum total bilirubin < 1.5 x IULN (an upper limit of bilirubin 5mg/dL is acceptable if it can be attributed to Gilbert's syndrome or erythropoiesis)
- •Serum creatinine < 2 x IULN or creatinine clearance > 50 mL/min by Cockcroft-Gault glomerular filtration rate estimation
- •The effects of ivosidenib on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (defined in Section 5.5) prior to study entry, for the duration of study participation, and for 90 days after the last dose of ivosidenib. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of the study, and for 90 days after the last dose of ivosidenib.
- •Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
排除标准
- •Indication of hematologic disease by bone marrow biopsy within 6 months of study entry.
- •*Evidence of disease progression from time of bone marrow biopsy to enrollment based on investigator review of symptoms and complete blood counts
- •Active malignancy (defined as > 1 cm disease on most recent CT scan in the past 6 months).
- •Currently receiving therapy for solid tumor malignancy.
- •Currently receiving any other investigational agents.
- •Known dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally.
- •A history of allergic reactions attributed to compounds of similar chemical or biologic composition to ivosidenib or other agents used in the study.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
- •Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 72 hours of study entry.
- •Heartrate corrected QT interval (QTc) > 450 msec or with other factors that increase the risk of QT prolongation or arrhythmic events (e.g. heart failure, hypokalemia, family history of long QT interval syndrome).
- •Known medical history of progressive multifocal leukoencephalopathy (PML).
- •Currently taking medications known to be CYP3A4 strong inducers and sensitive substrates.
研究组 & 干预措施
Ivosidenib
-Ivosidenib is an oral drug which will be administered on an outpatient basis at a dose of 500 mg daily for up to 5 years. Each cycle is 28 days.
干预措施: Ivosidenib (Drug)
结局指标
主要结局
Rate of improvement in hematologic parameters
时间窗: Through 30 days after completion of treatment (estimated to be 61 months)
Will be evaluated according to a modified version of the IWG 2006 Criteria for Hematologic Improvement for patients with MDS on clinical trials * Erythroid response (pretreatment, \<11 g/DL) * Hemoglobin (Hgb) increase by ≥1.5 g/dL * Relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 weeks, compared with the pretreatment transfusion number in the previous 8 weeks. Only RBC transfusions given for an Hgb of ≤9.0 g/dL pretreatment will count in the RBC transfusion response evaluation * Platelet response (pretreatment, \<100 x 10\^9/L) * Absolute increase of ≥30 × 10\^9/L for patients starting with \>20 × 10\^9/L platelets. * Increase from \<20 × 10\^9/L to \>20 × 10\^9/L and by at least 100%. * Neutrophil response (pretreatment, \<1.0 x 10\^9/L): * At least 100% increase and an absolute increase \>0.5 × 10\^9/L. If pegfilgrastim being used prior to initiation of study, define response as no longer requiring pegfilgrastim to maintain ANC \>500.
次要结局
- Change in mutant IDH1 variant allele fraction(Through completion of treatment (estimated to be 60 months))
- Disease free survival(Through 30 days after completion of treatment (estimated to be 61 months))
- Number of adverse events as measured by CTCAE v 5.0(Through 30 days after completion of treatment (estimated to be 61 months))
- Duration of hematologic response(Through completion of treatment (estimated to be 60 months))