A randomized study to evaluate the safety and efficacy of the two schedules of LDE225 in patients with acute leukemia

• Conditions: relapsed/refractory or untreated acute leukemia; Therapeutic area: Diseases [C] - Cancer [C04]; MedDRA version: 14.1Level: LLTClassification code 10000835Term: Acute leukemiaSystem Organ Class: 100000004864

• Registration Number: EUCTR2012-004022-21-IT
• Lead Sponsor: OVARTIS FARMA S.p.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-06-18
• Last Update Posted: 22 December 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 80

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 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

- Allogeneic SCT within the last 4 months and/or active GVHD, or autologous SCT within the last 4 weeks.
- 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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<br>2. To evaluate the safety and tolerability of two different dosing schedules of LDE225 in acute leukemia<br>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 Outcome Measures

Name	Time	Method
Secondary end point(s): 1. Overall Response Rate (ORR)<br>2. Safety (Adverse events, abnormal lab values, ECGs, SAEs etc.)<br>3. PK parameters:<br> - Tmax, Cmax, Ctrough, and AUC0-8h for all patients<br> - 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.