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

A Phase II Study of Oral Single Agent Panobinostat in Patients With Refractory de Novo or Secondary Acute Myelogenous Leukemia (AML)

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.

Study Overview

• Status: Completed
• Conditions: Acute Myelogenous Leukemia; Refractory Leukemia
• Intervention / Treatment: Drug: Panobinostat/LBH589

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Gosford, New South Wales, Australia, 2250
      • Novartis Investigative Site
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Novartis Investigative Site
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Novartis Investigative Site
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Novartis Investigative Site
    • Parkville, Victoria, Australia, 3002
      • Novartis Investigative Site
    • Prahran, Victoria, Australia, 3181
      • Novartis Investigative Site
• Belgium
  • Brugge, Belgium, 8000
    • Novartis Investigative Site
  • Gent, Belgium, 9000
    • Novartis Investigative Site
  • Liege, Belgium, 4000
    • Novartis Investigative Site
• France
  • Bobigny Cedex, France, 93009
    • Novartis Investigative Site
  • Montpellier cedex 5, France, 34295
    • Novartis Investigative Site
  • Nantes, France, 44035
    • Novartis Investigative Site
  • Paris Cedex 4, France, 75181
    • Novartis Investigative Site
  • Toulouse cedex 9, France, 31059
    • Novartis Investigative Site
• Germany
  • Frankfurt, Germany, 60590
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Nordrhein-Westfalen
    • Koeln, Nordrhein-Westfalen, Germany, 50937
      • Novartis Investigative Site
• Italy
  • RM
    • Roma, RM, Italy, 00161
      • Novartis Investigative Site
    • Roma, RM, Italy, 00133
      • Novartis Investigative Site
  • UD
    • Udine, UD, Italy, 33100
      • Novartis Investigative Site
• Korea, Republic of
  • Korea
    • Seoul, Korea, Korea, Republic of, 06591
      • Novartis Investigative Site
• Peru
  • Lima
    • Surquillo, Lima, Peru, 34
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Catalunya
    • Hospitalet de LLobregat, Catalunya, Spain, 08907
      • Novartis Investigative Site
• Switzerland
  • Bern, Switzerland, 3010
    • Novartis Investigative Site
  • Zürich, Switzerland, 8091
    • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Balcova / Izmir, Turkey, 35340
    • Novartis Investigative Site
• United Kingdom
  • Liverpool, United Kingdom, L7 8XP
    • Novartis Investigative Site
  • London, United Kingdom, W12 0HS
    • Novartis Investigative Site
  • London, United Kingdom, SE5 9RS
    • Novartis Investigative Site
  • Scotland
    • Aberdeen, Scotland, United Kingdom, AB25 2ZN
      • Novartis Investigative Site
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS9 7TF
      • Novartis Investigative Site
• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center Dept. of U. of Chicago Hosp(3)
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital Nebraska Methodist Hospital(2)
  • New York
    • Manhasset, New York, United States, 10030
      • North Shore University Hospital North Shore Univ
    • NY, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center Dept. of MSKCC (2)
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health Sciences University Dept. of OHSU (2)
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center Dept of Simmons Cancer Center
    • Houston, Texas, United States, 77030-4009
      • University of Texas/MD Anderson Cancer Center Dept of MD Anderson (14)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.	Drug: Panobinostat/LBH589

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Response as Per Investigator Assessment by Stratum (FAS)	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.	6 cycles of treatment with a 28-day treatment cycle (Day 168)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Partial Response Measured in Stratum A and B	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)	6 treatment cycles (28-day/treatment cycle)
Time to Remission Measured in Stratum A and B		6 treatment cycles (28-day/treatment cycle)
Duration of Remission Measured in Stratum A and B		6 treatment cycles (28-day/treatment cycle)
Event-free Survival Measured in Stratum A and B		6 treatment cycles (28-day/treatment cycle)
Overall Survival Measured in Stratum A and B		6 treatment cycles (28-day/treatment cycle)

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2009
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: March 30, 2009
• First Submitted That Met QC Criteria: April 10, 2009
• First Posted (Estimate): April 13, 2009

Study Record Updates

• Last Update Posted (Actual): February 23, 2017
• Last Update Submitted That Met QC Criteria: January 8, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: AML; Acute myeloid leukemia; refractory AML; relapsed acute myeloid leukemia; refractory de novo AML; refractory secondary AML; secondary AML; AML following myelodysplastic syndrome (MDS); AML following antecedent hematological disorder (AHD); AML resistant to therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Neoplastic Processes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasm Metastasis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Histone Deacetylase Inhibitors; Panobinostat
• Other Study ID Numbers: CLBH589B2213; 2008-002983-32 (EudraCT Number)