E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
MDS and AML in patients with high risk features after hemapoietic stem cell transplantation with reduced conditioning |
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E.1.1.1 | Medical condition in easily understood language |
Myelodyspastic Syndrome and Acute Myeloblastic Leukemia in patients with high risk features after stem cell transplantation with reduced conditioning |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
• 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)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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
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E.5 End points |
E.5.1 | Primary end point(s) |
Maximum tolerated dose (MTD) and dose-limiting toxicity (MTD) of panobinostat |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 28 days of administration |
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E.5.2 | 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
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E.5.2.1 | 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 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 7 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |