adverse risk AML or RAEB MedDRA version: 20.0 Level: LLT Classification code 10001941 Term: AML System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10037803 Term: RAEB System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Farydak 20 mg
Product Name: panobinostat
Pharmaceutical Form: Capsule
INN or Proposed INN: PANOBINOSTAT
CAS Number: 404950-80-7
Concentration unit: mg milligram(s)
Concentration type: equa
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
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 must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment; • Written informed consent. 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 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 15
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 |
|---|---|
| Main Objective: • To asses the safety and feasibility of post-transplant panobinostat combined with midostaurin in patients with adverse risk AML/RAEB with FLT3-ITD with high allelic ratio. ;Secondary Objective: To assess efficacy in terms of: • Complete hematological remission (with full peripheral blood recovery) rate at 3, 6 and 12 months post alloHSCT. • Immunological remission (residual disease assessed by multicolor flowcytometry) at 6 months post alloHSCT • 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. • OS from alloHSCT • 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, 12 months post alloHSCT To assess toxicity in terms of: • (serious) adverse events • 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 ;Primary end point(s): During dose finding: • Feasibility of protocol treatment as defined by the number of DLTs during the first cycle PNB/MST (see section 7.1). At final analysis: • Feasibility of protocol defined by the percentage of patients completing at least 6 cycles of combination therapy after having started protocol treatment ;Timepoint(s) of evaluation of this end point: During dose finding the number of DLT's will be continuously monitored The final analysis will tale place when the required data are available and evaluated | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • 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. • 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 ;Timepoint(s) of evaluation of this end point: Evaluation will take place when the required data are available and evaluated | — |
Countries
Belgium, Germany, Netherlands
Contacts
Public ContactHOVON Data Center
Erasmus MC, HOVON Data Center
Outcome results
None listed