Global study to find the recommended dose of HDM201 added to chemotherapy and to assess safety and efficacy in patients with newly diagnosed or relapsed/refractory acute myeloid leukemia
- Conditions
- Relapsed refractory (R/R) or newly diagnosed acute myeloid leukemia (AML)MedDRA version: 21.1Level: PTClassification code 10000880Term: Acute myeloid leukaemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003107-19-IT
- Lead Sponsor
- OVARTIS PHARMA AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 0
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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method