Study of Efficacy and Safety of LDE225 in Adult Patients With Relapsed/Refractory Acute Leukemia

Acute Leukemias Clinical Trial

Official title:

A Phase II Multi-center, Open Label, Randomized Study to Assess Safety and Efficacy of Two Different Schedules of Oral LDE225 in Adult Patients With Relapsed/Refractory or Untreated Elderly Patients With Acute Leukemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01826214
• Other study ID #: CLDE225X2203
• Status: Completed
• Phase: Phase 2
• First received: March 25, 2013
• Last updated: January 24, 2016
• Start date: May 2013
• Est. completion date: May 2015

Study information

• Verified date: January 2016
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The study will evaluate the efficacy, safety and tolerability of two dosing schedules of LDE225 in patients with relapsed/refractory acute leukemia or elderly patients with untreated acute leukemia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects must have relapsed or primary refractory non-M3 acute myeloid leukemia or relapsed or refractory non-T-cell acute lymphoblastic leukemia or untreated acute myeloid leukemia in elderly patients.

• Performance status of 0, 1 or 2 per WHO classification.

• Adequate renal and liver function.

• Adequate blood creatine kinase value (CK < 1.5ULN)

Exclusion Criteria:

• Allogeneic stem cell transplantation within the last 4 months and/or active graft versus host disease requiring systemic immunosuppressant therapy, or autologous stem cell transplantation within the last 4 weeks.

• Patient for which immediate allogeneic stem cell transplantation is the treatment of choice.

• Pregnant or nursing (lactating) women.

• Active CNS leukemic involvement

• Other protocol-defined inclusion/exclusion criteria may apply.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Disease
• Acute Leukemias
• Leukemia

Intervention

Drug:
• LDE225
LDE225 will be supplied as 200 mg capsules by Novartis. Patients will receive study treatment on an outpatient basis. LDE225 will be dispensed every two weeks for the first four weeks and at the start of every four weeks thereafter, as needed.

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Adelaide	South Australia
Australia	Novartis Investigative Site	Prahran	Victoria
Austria	Novartis Investigative Site	Salzburg
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Yvoir
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Ulm
Hungary	Novartis Investigative Site	Debrecen
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Nijmegen
Netherlands	Novartis Investigative Site	Rotterdam
Netherlands	Novartis Investigative Site	Rotterdam
Norway	Novartis Investigative Site	Bergen
Norway	Novartis Investigative Site	Trondheim
Spain	Novartis Investigative Site	Salamanca	Castilla y Leon
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
United Kingdom	Novartis Investigative Site	London
United States	Duke University Medical Center SC-5	Durham	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Germany,  Hungary,  Netherlands,  Norway,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of complete remission (CR) and complete remission with incomplete blood count recovery (CRi)	The primary efficacy endpoint is the rate of CR and CRi based on the International Working Group (IWG) criteria. Patients with acute leukemia will be randomized into one of two different dosing schedules of LDE225. Efficacy assessments will be performed to determine CR/CRi: every 8 weeks for 6 months post CR, and every 12 weeks thereafter.	Screening to 20 months	No
Secondary	Overall Response Rate (ORR) on two different dosing schedules of LDE225 in acute leukemia	ORR is the rate of CR, CRi or PR according to IWG criteria. CR, CRi or PR will be assessed through bone marrow biopsy/aspirate and peripheral blood blasts counts.	Every 8 weeks for the first 6 months and every 12 weeks until 53 weeks after the last patient is enrolled or until relapse	No
Secondary	Safety and tolerability of two different dosing schedules of LDE225 in acute leukemia	Safety and tolerability will be assessed based on the frequency of adverse events and number of laboratory values that fall outside of pre-determined ranges. Additional safety assessments include ECG, vital signs and SAEs.	Screening to 30 days post treatment discontinuation	Yes
Secondary	Characterization of the pharmacokinetics (PK) of two different dosing schedules of LDE225	PK parameters include: -Tmax, Cmax, Ctrough, and AUC0-8h for all patients; - AUC0-24h, CL/F and Racc for 800 mg QD arm only	Weekly for the first 9 weeks, Week 11, every 2 weeks until CR and every 4 weeks post CR	No