Acute myeloid leukemia AML MDS
Conditions
Interventions
This is a dose-escalation study of midostaurin (MST) in combination with a
fixed dose panobinostat in high allelic ratio FLT3-ITD positive AML. Patients
will receive panobinostat (PNB) at a starting
FLT3-ITD
Midostaurin
Panobinostat
Sponsors
HOVON
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: • Adult patients (18-70 years of age); • AML (except acute promyelocytic leukemia, AML M3 and bcr/abl positive AML) according to WHO 2016 classification or RAEB with IPSS-R > 4.5 with high mutant to wild-type allelic ratio of FLT3-ITD; • Newly diagnosed or in first relapse having obtained remission after induction chemotherapy; • First allogeneic HSCT scheduled within the next 2 months upon having achieved hematological remission ( 40%; • Negative serum pregnancy test for female patients of childbearing potential, at registration; • Female patients of childbearing potential and all men must be willing and able to use an effective contraceptive method during the study and for a minimum of 6 months after study treatment; • Written informed consent.
Exclusion criteria
Exclusion criteria: • Known HIV or HCV positivity; • History of active malignancy during the past 2 years with the exception of basal carcinoma of the skin or carcinoma *in situ* of the cervix or breast; • Pregnant or breast-feeding female patients; • Psychiatric disorder that interferes with ability to understand the study and give informed consent, and/or impacts study participation or follow-up;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Feasibility of protocol treatment as defined by the number of dose limiting toxicities (DLTs) during the first cycle of PNB/MST. | — |
Secondary
| Measure | Time frame |
|---|---|
| • Number of PNB/MST cycles given. • Complete hematological remission (with full peripheral blood recovery) rate at 3, 6 and 12 months post alloHSCT • MRD after PNB/MST cycle 3, or at 6 months post alloHSCT if patient goes off protocol treatment early. • Relapse/progression rate as assessed after cycle 1, 3, 5 and 7 and at 12 months post alloHSCT, or at approx. 3, 6 and 12 months post alloHSCT in case of early termination of protocol treatment.at 3, 6, and 12 months post alloHSCT • OS defined as the time from alloHSCT to death from any cause • PFS from alloHSCT with relapse (for patients in CR) and progression (for patients in PR) and death from any cause as events • Engraftment and chimerism at 3, 6, and 12 months post alloHSCT • (Serious) adverse events • The incidence and severity of acute and chronic GvHD up to 12 months post alloHSCT • NRM up to 12 months post alloHSCT • Number and percentage of registered patients starting protocol treatment) • Number and percentage of patients receiving post-transplant epigenetic therapy after alloHSCT and the duration of epigenetic treatment in patients who discontinue study treatment prematurely | — |
Countries
The Netherlands
Outcome results
None listed