EUCTR2018-003107-19-IT进行中（未招募）1 期
A phase I/II multi-center study of HDM201 added to chemotherapy in adult subjects with relapsed/refractory (R/R) or newly diagnosed acute myeloid leukemia (AML) -
适应症
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •All subjects
- •1. Signed informed consent must be obtained prior to participation in the study.
- •2. Age = 18 years at the date of signing the informed consent form (ICF).
- •3. Diagnosis of AML based on WHO 2016 classification (Arber et al 2016). Patients with APL (acute promyelocytic leukemia) with PMLRARA are not eligible.
- •4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) that is 0 to 2
- •5. Adequate organ functions:
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 3 × upper limit of normal (ULN)
- •Total bilirubin (TBL) = 1.5 × ULN (except in the setting of isolated Gilbert syndrome)
- •Glomerular Filtration Rate (estimation based on Cockcroft-Gault formula) = 30 mL/min
- •6. Left ventricular ejection fraction (LVEF) > 45% R/R AML subjects eligible for inclusion in this study must additionally meet the following criteria:
- •7. Diagnosis of relapsed or refractory AML
- •8. Suitable for treatment with intermediate dose cytarabine (IDAC) as per investigator judgement
- •9. For Part 3 only: willing and suitable to participate in DDI Cohort 1 or 2 1L AML subjects eligible for inclusion in this study must additionally meet the following criteria, as applicable to the part/cohort they are to
- •be enrolled in:
- •For Part 1 or Part 2 Expansion Cohort 1 or Part 2 Expansion Cohort 2 only:
- •10. Subjects with de novo AML
- •11. Suitable for induction treatment with cytarabine and anthracyclines as per investigator judgement
- •For Part 2 Expansion Cohort 2 only:
- •12. Documented presence of FLT3 mutation (ITD or TKD)
- •13. Suitable for midostaurin treatment as per investigator judgement
- •For Part 3 Expansion Cohort 3 only:
- •14. Subjects with secondary AML (e.g. AML with Myelodysplasia-Related Changes/AML-MRC, AML secondary to myelodysplasia/MDS or therapyrelated AML). Prior use of hypomethylating agents or other therapies
- •with curative intent for treating previous hematological malignancies or therapy-related AML is allowed.
- •15. Suitable for induction treatment with liposomal cytarabine/daunorubicin as per investigator judgement
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 135
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of subjects for this age range 45
排除标准
- •1. Prior exposure to MDM2 and MDM4 inhibitor (eg, idasanutlin)
- •2. Known CNS leukemia with signs or symptoms that are not controlled by adequate therapy.
- •3. Isolated extramedullary leukemia
- •4. For Part 1 only: subjects with a known favorable-risk AML subtype at screening
- •5. For Part 1 only: subjects with documented FLT3 mutation.
- •6. Subjects with prior malignancy, except for: a) Adequately treated solid tumor for which the subject has been disease free for at least 2 years and if no anticancer therapy is ongoing or required during the
- •course of the study; b) Subjects with history of hematological malignancies leading to secondary AML (eg, myelodysplasia/myelodysplastic syndrome (MDS)) and subjects with therapy-related
- •AML will not be excluded in dose Expansion Cohort 3.
- •7. Any concurrent severe and/or uncontrolled medical condition eg, a) cardiovascular disease including congestive heart failure, or b) active uncontrolled infection requiring parenteral antibacterial, antiviral or
- •antifungal therapy compromised by hemodynamic instability
- •8. QTcF > 470 ms at screening
- •9. Any other known disease that could compromise participation in the study including gastrointestinal (GI) disorders impacting absorption of HDM201, evidence of major active bleeding or history of bleeding
- •diathesis or major coagulopathy not related to AML
- •10. Known confirmed diagnosis of human immunodeficiency virus (HIV) infection
- •11. Evidence of active hepatitis B (HBV) or hepatitis C (HCV) viral infection (hepatitis B surface antigen (HBsAg) in the absence of hepatitis B surface antibody (HBsAb) OR HCV Ab (antibody) positive with HCV
- •RNA (ribonucleic acid) positive)
- •12. Subjects who require treatment with moderate or strong CYP3A4 inducers within 14 days prior to starting study treatment, or are expected to receive moderate or strong CYP3A4 inducers during the
- •entire study
- •13. Subjects who require the use of herbal preparations/medications and dietary supplements (except for vitamins) within 7 days prior to first dose of study treatment or are expected to use such products during the
- •entire study
- •14. Subjects who require treatment with substrates of CYP3A4/5 with a narrow therapeutic index (within 24 hours prior to, during and 48 hours after HDM201 administration).
- •15. Subjects taking medications with a known risk of prolonging the QT interval or inducing Torsade de pointes, if such medication cannot be discontinued or replaced safely with an alternative medication prior to
- •starting first dose of HDM201
- •16. Subjects who require treatment with moderate or strong CYP3A4 inhibitors within 48 hours prior to, during and 48 hours post HDM201 administration. Of note, this is not applicable for Part 3 Cycle 1
- •17. Subject is pregnant or breastfeeding
- •18. Women of child-bearing potential
- •19. Sexually active males unless they use a condom during intercourse while taking study drug and for 2 weeks after HDM201 discontinuation or for 4 months after midostaurin discontinuation (for 1L AML Expansion
- •Cohort 2 only) or for 6 months after liposomal cytarabine/daunorubicin (for 1L AML Expansion Cohort 3 only) and thus do not attempt to 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.
- •Additional exclusion criteria apply for R/R AML subjects and for 1L AML subjects as per protocol
研究者
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