relapsed/refractory or untreated acute leukemia MedDRA version: 16.1 Level: LLT Classification code 10000835 Term: Acute leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: LDE225
Pharmaceutical Form: Capsule
INN or Proposed INN: sonidegib
CAS Number: 1218778-77-8
Current Sponsor code: LDE225
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
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. 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 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: - Allogeneic SCT within the last 4 months and/or active GVHD which requires systemic immunosuppressant therapy, or autologous SCT within the last 4 weeks. - Patient 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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; Secondary Objective: 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 ;Primary end point(s): Rate of CR and CRi;Timepoint(s) of evaluation of this end point: As defined in Table 3-1 and section 10.4.2 of the protocol. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 ;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. | — |
Countries
Australia, Austria, Belgium, Canada, France, Germany, Hungary, Ireland, Italy, Netherlands, Norway, Russian Federation, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactMedical Collaboration Centre
Novartis Pharmaceuticals UK Ltd
Outcome results
None listed