A phase 3, multicenter, open-label, randomized, study of gilteritinib versus midostaurin in combination with induction and consolidation therapy followed by one-year maintenance in patients with newly diagnosed Acute Myeloid Leukemia (AML) or Myelodysplastic syndromes with excess blasts-2 (MDS-EB2) with FLT3 mutations eligible for intensive chemotherapy - HOVON 156 AML / AMLSG 28-18

HOVO0 个研究点目标入组 250 人开始时间: 待定最近更新: 2024年9月9日

适应症

试验速览

阶段: 3 期
状态: 已完成
发起方
入组人数: 250

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

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研究设计

研究类型: Interventional

入排标准

年龄范围: 18 至 99（—）

入选标准

•Age >=18 years
•Newly diagnosed AML or MDS with excess of blasts-2 (EB2) defined according to
•WHO criteria (appendix A), with centrally documented FLT3 gene mutation (either
•TKD or ITD or both). AML may be secondary to prior hematological disorders,
•including MDS, and/or therapy-related. Patients may have had previous treatment
•with erythropoiesis stimulating agents (ESA) for MDS. ESA have to be stopped
•at least four weeks before registration
•FLT3 mutation as assessed by DNA fragment analysis PCR for FLT3-ITD and
•FLT3-TKD mutation. Positivity is defined as a FLT3-ITD or FLT3-TKD / FLT3-WT
•ratio of >= 0.05 (5%).
•Considered to be eligible for intensive chemotherapy
•Patient is suitable for oral administration of study drug
•WHO/ECOG performance status <= 2
•Adequate hepatic function as evidenced by
•o Serum total bilirubin <= 2.5 × upper limit of normal (ULN) unless considered
•due to leukemic involvement following written approval by the (co) Principal
•Investigator
•o Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and
•alkaline phosphatase (ALP) <= 3.0 × ULN, unless considered due to leukemic
•involvement following written approval by the (co) Principal Investigator
•Adequate renal function as defined by creatinine clearance > 40 mL/min based
•on the Cockroft-Gault glomerular filtration rate (GFR)
•Written informed consent
•Patient is capable of giving informed consent
•Female patient must either:
•o Be of nonchildbearing potential:
•* Postmenopausal (defined as at least 1 year without any menses) prior to
•screening, or
•* Documented surgically sterile or status posthysterectomy (at least 1 month
•prior to screening)
•o Or, if of childbearing potential,
•* Agree not to try to become pregnant during the study and for 6 months after
•the final study drug administration
•* And have a negative urine or serum pregnancy test at screening
•* And, if heterosexually active, agree to consistently use highly effective*
•contraception per locally accepted standards in addition to a barrier method
•starting at screening and throughout the study period and for 6 months after
•the final study drug administration.
•*Highly effective forms of birth control include:
•Consistent and correct usage of established hormonal contraceptives that
•inhibit ovulation,
•Established intrauterine device (IUD) or intrauterine system (IUS),
•Bilateral tubal occlusion,
•Vasectomy (A vasectomy is a highly effective contraception method provided
•the absence of sperm has been confirmed. If not, an additional highly
•effective method of contraception should be used.)
•Male is sterile due to a bilateral orchiectomy.
•Sexual abstinence is considered a highly effective method only if defined as
•refraining from heterosexual activity during the entire period of risk
•associated with the study drug. The reliability of sexual abstinence needs to
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排除标准

•Prior chemotherapy for AML or MDS-EB2, including prior treatment with
•hypomethylating agents. Hydroxyurea is allowed for the control of peripheral
•leukemic blasts in patients with leukocytosis (e.g., white blood cell [WBC]
•counts > 30 x 10^9/L)
•Acute promyelocytic leukemia (APL) with PML-RARA or one of the other
•pathognomonic variant fusion genes/chromosome translocations
•Blast crisis after CML
•Known or suspected hypersensitivity to midostaurin or gilteritinib and/or any
•Patient requires treatment with concomitant drugs that are strong inducers of
•cytochrome P450 (CYP) 3A
•Breast feeding at start of study treatment
•Active infection, including hepatitis B or C or HIV infection that is
•uncontrolled at randomization. An infection controlled with an approved or
•closely monitored antibiotic/antiviral/antifungal treatment is allowed.
•Patients with a currently active second malignancy. Patients are not
•considered to have a currently active malignancy if they have completed therapy
•and are considered by their physician to be at less than 30% risk of relapse
•within one year. However, patients with the following history/concurrent
•conditions are allowed:
•o Basal or squamous cell carcinoma of the skin;
•o Carcinoma in situ of the cervix;
•o Carcinoma in situ of the breast;
•o Incidental histologic finding of prostate cancer
•Significant active cardiac disease within 6 months prior to the start of
•study treatment, including:
•o New York Heart Association (NYHA) Class III or IV congestive heart failure;
•o Myocardial infarction;
•o Unstable angina and/or stroke;
•o Left ventricular ejection fraction (LVEF) < 40% by ECHO or MUGA scan obtained
•within 28 days prior to the start of study treatment
•QTc interval using Fridericia*s formula (QTcF) >= 450 msec (average of
•triplicate determinations) or other factors that increase the risk of QT
•prolongation or arrhythmic events (e.g., heart failure, family history of long
•QT interval syndrome). Prolonged QTc interval associated with bundle branch
•block or pacemaking is permitted with written approval of the (co) Principal
•Investigator.
•Patient with hypokalemia and/or hypomagnesemia before registration (defined
•as values below LLN) Note: electrolyte suppletion is allowed to correct LLN
•values before registration.
•Dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit
•the ingestion or gastrointestinal absorption of orally administered drugs
•Clinical symptoms suggestive of active central nervous system (CNS) leukemia
•or known CNS leukemia. Evaluation of cerebrospinal fluid (CSF) during screening
•is only required if there is a clinical suspicion of CNS involvement by
•leukemia during screening
•Immediate life-threatening, severe complications of leukemia such as
•uncontrolled bleeding and/or disseminated intravascular coagulation
•Any other medical or psychological condition deemed by the Investigator to be
•likely to interfere with a patient*s ability to give informed consent or
•participate in the study
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研究者

发起方

HOVO

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