E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
relapsed/refractory or untreated acute leukemia |
|
E.1.1.1 | Medical condition in easily understood language |
relapsed/refractory or untreated acute leukemia |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000835 |
E.1.2 | Term | Acute leukemia |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the rate of complete remission (CR) and complete remission with incomplete blood count recovery (CRi) on two different dosing schedules of LDE225 in acute leukemia |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the Overall Response Rate on two different dosing schedules of LDE225 in acute leukemia 2. To evaluate the safety and tolerability of two different dosing schedules of LDE225 in acute leukemia 3. To further characterize the pharmacokinetics of two different dosing schedules of LDE225 in acute leukemia |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female adult patients (≥18 years). - Histological or cytological diagnosis of either relapsed or primary refractory non-M3 acute myeloid leukemia (AML); untreated AML in patients ≥ 65 years of age, if they are not candidates for standard induction chemotherapy; or have failed alternative therapies (such as decitabine, azacitidine, etc.) -relapsed or refractory non-T-cell acute lymphoblastic leukemia (ALL) - White blood cell count (WBC) ≤ 50 x 109/L. - Performance status corresponding to ECOG (WHO) score of 0, 1 or 2. - Adequate renal function - Adequate liver function - Serum CK ≤ 1.5 x ULN. - At least 2 weeks since end of last leukemia therapy.
Other protocol defined inclusion criteria may apply. |
|
E.4 | Principal exclusion criteria |
- Allogeneic SCT within the last 4 months and/or active GVHD which requires systemic immunosuppresant therapy, or autologous SCT within the last 4 weeks. - Patientes for which immediate allogenic SCT is the treatment of choice. - Patients with a life threatening or uncontrolled systemic infection. - Active CNS leukemic involvement. - Major surgery within 2 weeks of initiation of study medication. - Concurrent uncontrolled medical conditions that may interfere or potentially affect the interpretation of the study. - Unable to take oral drugs, or lack of physical integrity of the upper gastrointestinal tract, or known malabsorption syndromes. - Patients with unresolved diarrhea > CTCAE grade 2. - Patients who have previously been treated with systemic LDE225 or with other Hh pathway inhibitors. - Patients who have neuromuscular disorders or are on concomitant treatment with drugs that are recognized to cause rhabdomyolysis - patients who are planning on embarking on new physical activities, such as strenuous exercise, that can result in significant increases in plasma CK levels while on study treatment. - Patient has history of cardiac dysfunction - patient has active cardiac disease - Use of other investigational drugs within 30 days or 5 half-lives of initiation of study medication, whichever is longer. - Patients who are receiving treatment with medications known to be moderate and strong inhibitors or inducers of CYP3A4/5 or drugs metabolized by CYP2B6 or CYP2C9 that have narrow therapeutic index, and that cannot be discontinued before starting treatment with LDE225. - Patients are excluded if the use of warfarin is necessary and cannot be substituted - Pregnant or nursing (lactating) women - Patients who are not willing to apply highly effective contraception during the study and the defined duration after final dose of study treatment. - Known HIV positivity.
Other protocol defined exclusion criteria may apply. |
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E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
As defined in Table 3-1 and section 10.4.2 of the protocol. |
|
E.5.2 | Secondary end point(s) |
1. Overall Response Rate (ORR) 2. Safety (Adverse events, abnormal lab values, ECGs, SAEs etc.) 3. PK parameters: - Tmax, Cmax, Ctrough, and AUC0-8h for all patients - AUC0-24h, CL/F and Racc for 800 mg QD arm only |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
As defined in Table 3-1 and sections 10.5., 10.5.2 and 10.5.3 of the protocol. |
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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 | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
two treatment schedules of LDE225 |
|
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Canada |
France |
Italy |
Netherlands |
Norway |
Sweden |
Australia |
Germany |
Hungary |
Spain |
Russian Federation |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 9 |