Efficacy and Safety of Panobinostat (LBH589) in Patients With Refractory de Novo or Secondary Acute Myelogenous Leukemia (AML)

Tracking Information
First Submitted Date ICMJE	March 30, 2009
First Posted Date ICMJE	April 13, 2009
Results First Submitted Date	July 21, 2016
Results First Posted Date	September 9, 2016
Last Update Posted Date	February 23, 2017
Study Start Date ICMJE	August 2009
Actual Primary Completion Date	February 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: January 8, 2017)	Best Response as Per Investigator Assessment by Stratum (FAS) [ Time Frame: 6 cycles of treatment with a 28-day treatment cycle (Day 168) ]; Response to treatment was defined as complete remission rate (CRR). CRR is complete remission (CR) and morphologic CR with incomplete blood count recovery (residual neutropenia or thrombocytopenia) (CRi). To stop or to proceed with Stage 2 of a given stratum of the Simon's optimal 2-stage design was based on the number of patients with CR/CRi and a safety evaluation of the patients from Stage 1 in that stratum. If early results clearly indicated that the drug was not active or worthy of further investigation, enrollment of that particular stratum would be terminated. CR and CRi were assessed by the Investigator according to IWG response Criteria for AML (Cheson et al 2003). As per protocol we would continue to stage II if ≥ 4 patients out of 26 patients enrolled to stage I had a CR or a CRi. As per response observed there was only 1 patient with CR/CRi in stratum A and 2 patients with CR/CRi in Stratum B.
Original Primary Outcome Measures ICMJE; (submitted: April 10, 2009)	CRR [complete remission rate (CR/CRi)] [ Time Frame: 6 months ]
Change History	Complete list of historical versions of study NCT00880269 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: January 8, 2017)	Partial Response Measured in Stratum A and B [ Time Frame: 6 treatment cycles (28-day/treatment cycle) ]As predefined in the study's protocol, stage II was not pursued due to lack of activity (at end of stage I less than 4 patients in each stratum with CR/CRi); Time to Remission Measured in Stratum A and B [ Time Frame: 6 treatment cycles (28-day/treatment cycle) ]; Duration of Remission Measured in Stratum A and B [ Time Frame: 6 treatment cycles (28-day/treatment cycle) ]; Event-free Survival Measured in Stratum A and B [ Time Frame: 6 treatment cycles (28-day/treatment cycle) ]; Overall Survival Measured in Stratum A and B [ Time Frame: 6 treatment cycles (28-day/treatment cycle) ]
Original Secondary Outcome Measures ICMJE; (submitted: April 10, 2009)	To assess partial remission [ Time Frame: duration of study/after end of study ]; Time to remission and duration of remission [ Time Frame: duration of study ]; Event-free survival [ Time Frame: duration of study/after end of study ]; Overall survival [ Time Frame: duration of study/after end of study ]; safety and tolerability [ Time Frame: duration of study ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Efficacy and Safety of Panobinostat (LBH589) in Patients With Refractory de Novo or Secondary Acute Myelogenous Leukemia (AML)
Official Title ICMJE	A Phase II Study of Oral Single Agent Panobinostat in Patients With Refractory de Novo or Secondary Acute Myelogenous Leukemia (AML)
Brief Summary	This study was to evaluate the efficacy and safety of single agent oral panobinostat in patients who have refractory de novo or refractory secondary AML.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Refractory Leukemia; Acute Myelogenous Leukemia
Intervention ICMJE	Drug: Panobinostat/LBH589
Study Arms	Experimental: Stratum A patients with refractory acute myelogenous leukemia (AML) initially diagnosed as de novo AML received 60 mg of panobinostat per day on three discontinuous days per week. Intervention: Drug: Panobinostat/LBH589; Experimental: Stratum B patients with refractory AML initially diagnosed as AML secondary to myelodysplastic syndrome (MDS)/antecedent hematologic disorder (AHD) received 60 mg of panobinostat per day on three discontinuous days per week. Intervention: Drug: Panobinostat/LBH589
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: July 21, 2016)	59
Original Estimated Enrollment ICMJE; (submitted: April 10, 2009)	164
Actual Study Completion Date	February 2012
Actual Primary Completion Date	February 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Written informed consent prior to study-specific screening procedures; Life expectancy of ≥ 60 days; Eastern Cooperative Group (ECOG) performance status ≤ 2; Refractory AML with confirmed initial diagnosis of de novo AML (excluding APL) - OR- Refractory AML with confirmed initial diagnosis of AML (excluding APL) secondary to AHD or MDS with either condition precedent to AML (MDS/AHD); Negative serum pregnancy test (within 7 days of first dose); Negative urine pregnancy test immediately prior to first dose Exclusion Criteria: Known HIV; Psychiatric disorder that interfered with ability to understand the study and give informed consent, and/or would impact study participation or follow-up; Concurrent use of medications that might prolong the QT interval or of inducing Torsade de Pointes; Female patients who were pregnant or breast-feeding or patients of childbearing potential who were not willing to use a double barrier method of contraception during the study and for 3 months following the last dose of study drug.; Male patients whose sexual partner(s) were women of childbearing potential who were not willing to use a double method of contraception, one of which included a condom, during the study and for 3 months after the end of treatment; Patient unable to swallow capsules; Patients with impaired gastrointestinal systems which might cause interference with digesting and absorbing panobinostat Other Protocol-defined inclusion/exclusion criteria may apply
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 85 Years (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Australia, Belgium, France, Germany, Italy, Korea, Republic of, Peru, Spain, Switzerland, Turkey, United Kingdom, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00880269
Other Study ID Numbers ICMJE	CLBH589B2213; 2008-002983-32 ( EudraCT Number )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Novartis ( Novartis Pharmaceuticals )
Study Sponsor ICMJE	Novartis Pharmaceuticals
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account	Novartis
Verification Date	January 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP