MDS and AML in patients with high risk features after hemapoietic stem cell transplantation with reduced conditioning
Conditions
Interventions
Product Name: Panobinostat
Product Code: LBH 589
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Panobinostat
Current Sponsor code: LBH589
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Goethe Universität Frankfurt
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • AML (except acute promyelocytic leukemia, AML M3) 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 15 of the first induction cycle - adverse risk cytogenetics including complex karyotype (= 3 abnormalities or abnormalities of chromosomes 3, 5 or 7) regardless of stage - secondary to MDS or radio-/chemotherapy or • MDS RAEB according to the WHO classification or intermediate-2 or high-risk according to IPSS or • CMML with = 5% bone marrow blasts and • Allogeneic HSCT with reduced intensity conditioning performed within 60 - 150 days prior to study entry • Complete hematologic remission documented by bone marrow aspiration within 28 days prior to study entry 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 31 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 31
Exclusion criteria
Exclusion criteria: • Active acute GvHD overall grade 2 - 4 • Prior treatment with a DAC inhibitor • Concomittant antileukemic medication • Patients with impaired cardiac function or other concurrent severe and/or uncontrolled medical conditions • Clinical symptoms suggesting CNS leukemia • Patient has an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of Panobinostat when administered within 150 days after HSCT and given in conjunction with standard immunosuppressive therapy after HSCT for patients with high-risk MDS or AML;Secondary Objective: • To determine safety and tolerability of panobinostat • To determine overall and disease-free survival at 12 months after HSCT • To evaluate immunoregulatory properties of panobinostat • To evaluate patient-reported health-related quality of life (HRQL) ;Primary end point(s): Maximum tolerated dose (MTD) and dose-limiting toxicity (MTD) of panobinostat ;Timepoint(s) of evaluation of this end point: after 28 days of administration | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Safety and tolerability as determined by type, frequency, severity and relationship of adverse events to study treatment • Cumulative incidence of hematologic relapse and death at one year after HSCT • Cumulative incidence of severe acute GvHD and extensive chronic GvHD at one year after HSCT • Reconstitution of the immune system as measured by changes in numbers, ratio, phenotype and activation state of peripheral blood cell populations during panobinostat therapy • Time to and duration of complete donor chimerism • HRQL at baseline, day 85, and 28 days after last intakte of study drug ;Timepoint(s) of evaluation of this end point: if not other specified above: after one year of administration and one additional year of follow-up | — |
Countries
Germany
Contacts
Public ContactStudy Centre Hematology
Universitätsklinikum Frankfurt
Outcome results
None listed