A Phase 1b/2 Study of TP-0903 in Patients With Acute Myeloid Leukemia and FLT3 Mutations
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Composite complete response (CR) rate
研究概览
简要总结
This phase IB/II trial studies the best dose of TP-0903 and how well it works when given alone or with azacitidine in treating patients with FLT3 gene mutated acute myeloid leukemia. TP-0903 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving TP-0903 alone or with azacitidine may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine a tolerable dose of dubermatinib (TP-0903) monotherapy for relapsed/refractory patients with FLT3 acute myeloid leukemia (AML).
II. To determine the maximum tolerated dose (MTD) of TP-0903 with azacitidine in untreated unfit patients with FLT3 AML.
III. To determine the complete remission (CR) or complete remission with partial hematologic recovery (CRh) rate following induction therapy with TP-0903 in relapsed/refractory patients or TP-0903 with azacitidine therapy in untreated unfit patients with FLT3 AML.
SECONDARY OBJECTIVES:
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 with AML and the presence of FLT3-ITD mutation
- •Patients with secondary AML or therapy related disease (t-AML) are eligible
- •If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 6 months
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Total bilirubin < 2.0mg/dL unless due to Gilbert's disease
- •Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional upper limit of normal
- •Creatinine (Cr) clearance > 50 mL/min by Cockcroft-Gault calculation
- •New York Heart Association (NYHA) Congestive Heart Failure (CHF) class II or better
- •Cardiac ejection fraction ≥40%
- •Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose
- •Ability to understand and willingness to sign the written informed consent document
- •Human immunodeficiency virus (HIV) infection without history of acquired immunodeficiency syndrome (AIDS) and sufficiently high CD4 cells (> 400/mm^3) and low HIV viral loads (< 30,000 copies/ml plasma) not requiring anti-HIV therapy are eligible
排除标准
- •Patients with acute promyelocytic leukemia
- •Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. Treatment with hydoxyurea is permitted during cycle 1 to maintain white blood cell (WBC) < 40,000/uL
- •Patients receiving any other investigational agents or patients that have received other investigational agents within 14 days of enrollment
- •Patients with active central nervous system (CNS) malignancy
- •Major surgery within 2 weeks before day 1
- •Uncontrolled active infection. Patients with infection requiring parenteral antibiotics are eligible if the infection is controlled
- •Patients with significantly diseased or obstructed gastrointestinal tract
- •Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, myocardial infarction within 6 months prior to enrollment, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any electrocardiogram (ECG) abnormality at screening has to be documented by the investigator as not medically relevant
- •Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
- •Pregnant women or women who are breastfeeding are excluded from this study. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women
- •Patients with advanced malignant solid tumors
- •Patients who are not able to swallow capsules or tablets
研究组 & 干预措施
Treatment (dubermatinib)
FLT3 AML WITH RELAPSED/REFRACTORY DISEASE:
INDUCTION: Patients receive dubermatinib PO QD on days 1-21. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients with clinical or hematologic response and not transplant eligible may continue dubermatinib until loss of response/clinical benefit. Patients with clinical or hematologic response and transplant eligible may continue dubermatinib until one week prior to admission.
干预措施: Azacitidine (Drug)
Treatment (dubermatinib)
FLT3 AML WITH RELAPSED/REFRACTORY DISEASE:
INDUCTION: Patients receive dubermatinib PO QD on days 1-21. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
MAINTENANCE: Patients with clinical or hematologic response and not transplant eligible may continue dubermatinib until loss of response/clinical benefit. Patients with clinical or hematologic response and transplant eligible may continue dubermatinib until one week prior to admission.
干预措施: Dubermatinib (Drug)
结局指标
主要结局
Composite complete response (CR) rate
时间窗: Up to 5 years post registration
Will calculate the composite CR rate (complete remission \[CR\]/complete remission with incomplete count recovery \[CRh) defined according to the 2017 European LeukemiaNet Acute Myeloid Leukemia recommendation.
Composite CR rate with partial hematologic recovery (CRh) rate
时间窗: through study completion, an average of 1 year
Will calculate the composite CR rate (CR/CRh), defined according to the International Working Group criteria and assessed at the end of induction.
Maximum tolerated dose of dubermatinib (TP-0903)
时间窗: Up to 28 days
Determine a tolerable dose of TP-0903 monotherapy for relapsed/refractory patients with FLT3 AML.
次要结局
- Disease-free survival(From the date of first CR/CRh until the first date of relapse/progression or death from any cause, assessed up to 5 years post registration)
- The Number of patients who proceed to transplant(Up to 5 years post registration)
- Maximum grade of each type of adverse event(Up to 5 years post registration)
- Incidence of treatment-related adverse events(Up to 5 years post registration)
- Tolerability of TP-0903(Up to 5 years post registration)
- Overall survival(From the treatment start date until the date of death from any cause or date last known alive, assessed up to 5 years post registration)
研究者
Uma Borate
Principal Investigator
Ohio State University Comprehensive Cancer Center