acute myeoloid leukemia myelodysplasia
Conditions
Interventions
Patients will receive panobinostat at a starting dose of 20 mg, once a day,
three days per week, every other week. Study treatment will be started within 7
days after randomization and continued for
Sponsors
Goethe Unversität, Frankfurt, Main, Germany
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: - Adult patients (18-70 years of age) - AML (except acute promyelocytic leukemia with PML-RARA and AML with BCR-ABL1) according to WHO 2016 classification with high-risk features defined as one or more of the following criteria: - refractory to or relapsed after at least one cycle of standard chemotherapy - > 10% bone marrow blasts at day 14-21 of the first induction cycle - adverse risk according to ELN 2017 risk stratification by genetics regardless of stage - secondary to MDS or radio-/chemotherapy - MRD positive before HSCT based on flow cytometry or PCR or, - MDS with excess blasts (MDS-EB) according to the WHO 2016 classification, or high-risk or very high-risk according to IPSS-R
Exclusion criteria
Exclusion criteria: - Active acute GvHD grade III-IV according to modified Glucksberg criteria - Active acute GvHD grade II or chronic GvHD moderate/severe according to NIH criteria requiring systemic corticosteroids > 0.5 mg/kg body weight of methylprednisolone equivalent or combination immunosuppressive treatment - Uncontrolled or significant heart disease, including recent myocardiac infarction, cardiac failure (NYHA II-IV), unstable angina pectoris, or clinically significant bradycardia - Long QT syndrome - QTcF >=*480 msec on screening ECG to be performed within 14 days prior to enrollment - Concurrent use of medications that have a relative risk of prolonging QT interval or of inducing Torsade de Pointes, if such treatment cannot be discontinued or switched to a different medication prior to the first dose of study drug. - Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes mellitus, chronic obstructive or chronic restrictive pulmonary disease including dyspnoea at rest from any cause) or history of serious organ dysfunction or disease involving the heart, kidney, or liver and/or seropositive HIV or HCV . - Serious active infection - CMV reactivation, which is not responsive to first-line valganciclovir or ganciclovir - Impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or small bowel resection). - Pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival | — |
Secondary
| Measure | Time frame |
|---|---|
| - Event-free survival (EFS) - Disease-free survival (DFS) - Cumulative incidence of hematologic relapse - Cumulative incidence, time and cause of non-relapse mortality - Cumulative incidence of new onset or aggravation of acute GvHD grade III-IV - Cumulative incidence and maximal grade of severity of chronic GvHD requiring systemic treatment within one year after HSCT - Percentage of patients who are free of systemic immunosuppressive therapy at one and two years after HSCT - Percentage of patients completing the one year study treatment and duration of panobinostat administration in patients who discontinue study treatment prematurely - Percentage of patients with MRD conversion from baseline to 6 months after HSCT - Patient-reported HRQoL during panobinostat maintenance therapy | — |
Countries
Netherlands
Outcome results
None listed