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

Primary Purpose

Refractory Leukemia, Acute Myelogenous Leukemia

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Panobinostat/LBH589
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Refractory Leukemia focused on measuring Acute myeloid leukemia, AML, relapsed acute myeloid leukemia, refractory AML, refractory de novo AML, refractory secondary AML, secondary AML, AML following myelodysplastic syndrome (MDS), AML following antecedent hematological disorder (AHD), AML resistant to therapy

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Chicago Medical Center Dept. of U. of Chicago Hosp(3)
  • Nebraska Methodist Hospital Nebraska Methodist Hospital(2)
  • North Shore University Hospital North Shore Univ
  • Memorial Sloan Kettering Cancer Center Dept. of MSKCC (2)
  • Oregon Health Sciences University Dept. of OHSU (2)
  • University of Texas Southwestern Medical Center Dept of Simmons Cancer Center
  • University of Texas/MD Anderson Cancer Center Dept of MD Anderson (14)
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Stratum A

Stratum B

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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)
Time to Remission Measured in Stratum A and B
Duration of Remission Measured in Stratum A and B
Event-free Survival Measured in Stratum A and B
Overall Survival Measured in Stratum A and B

Full Information

First Posted
March 30, 2009
Last Updated
January 8, 2017
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00880269
Brief Title
Efficacy and Safety of Panobinostat (LBH589) in Patients With Refractory de Novo or Secondary Acute Myelogenous Leukemia (AML)
Official Title
A Phase II Study of Oral Single Agent Panobinostat in Patients With Refractory de Novo or Secondary Acute Myelogenous Leukemia (AML)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
August 2009 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
February 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Leukemia, Acute Myelogenous Leukemia
Keywords
Acute myeloid leukemia, AML, relapsed acute myeloid leukemia, refractory AML, refractory de novo AML, refractory secondary AML, secondary AML, AML following myelodysplastic syndrome (MDS), AML following antecedent hematological disorder (AHD), AML resistant to therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
59 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Stratum A
Arm Type
Experimental
Arm Description
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.
Arm Title
Stratum B
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Panobinostat/LBH589
Primary Outcome Measure Information:
Title
Best Response as Per Investigator Assessment by Stratum (FAS)
Description
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.
Time Frame
6 cycles of treatment with a 28-day treatment cycle (Day 168)
Secondary Outcome Measure Information:
Title
Partial Response Measured in Stratum A and B
Description
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 Frame
6 treatment cycles (28-day/treatment cycle)
Title
Time to Remission Measured in Stratum A and B
Time Frame
6 treatment cycles (28-day/treatment cycle)
Title
Duration of Remission Measured in Stratum A and B
Time Frame
6 treatment cycles (28-day/treatment cycle)
Title
Event-free Survival Measured in Stratum A and B
Time Frame
6 treatment cycles (28-day/treatment cycle)
Title
Overall Survival Measured in Stratum A and B
Time Frame
6 treatment cycles (28-day/treatment cycle)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of Chicago Medical Center Dept. of U. of Chicago Hosp(3)
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Nebraska Methodist Hospital Nebraska Methodist Hospital(2)
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68114
Country
United States
Facility Name
North Shore University Hospital North Shore Univ
City
Manhasset
State/Province
New York
ZIP/Postal Code
10030
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center Dept. of MSKCC (2)
City
NY
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Oregon Health Sciences University Dept. of OHSU (2)
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Texas Southwestern Medical Center Dept of Simmons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
University of Texas/MD Anderson Cancer Center Dept of MD Anderson (14)
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4009
Country
United States
Facility Name
Novartis Investigative Site
City
Gosford
State/Province
New South Wales
ZIP/Postal Code
2250
Country
Australia
Facility Name
Novartis Investigative Site
City
Herston
State/Province
Queensland
ZIP/Postal Code
4029
Country
Australia
Facility Name
Novartis Investigative Site
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Facility Name
Novartis Investigative Site
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
3065
Country
Australia
Facility Name
Novartis Investigative Site
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3002
Country
Australia
Facility Name
Novartis Investigative Site
City
Prahran
State/Province
Victoria
ZIP/Postal Code
3181
Country
Australia
Facility Name
Novartis Investigative Site
City
Brugge
ZIP/Postal Code
8000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Novartis Investigative Site
City
Bobigny Cedex
ZIP/Postal Code
93009
Country
France
Facility Name
Novartis Investigative Site
City
Montpellier cedex 5
ZIP/Postal Code
34295
Country
France
Facility Name
Novartis Investigative Site
City
Nantes
ZIP/Postal Code
44035
Country
France
Facility Name
Novartis Investigative Site
City
Paris Cedex 4
ZIP/Postal Code
75181
Country
France
Facility Name
Novartis Investigative Site
City
Toulouse cedex 9
ZIP/Postal Code
31059
Country
France
Facility Name
Novartis Investigative Site
City
Koeln
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
50937
Country
Germany
Facility Name
Novartis Investigative Site
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00133
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
State/Province
RM
ZIP/Postal Code
00161
Country
Italy
Facility Name
Novartis Investigative Site
City
Udine
State/Province
UD
ZIP/Postal Code
33100
Country
Italy
Facility Name
Novartis Investigative Site
City
Seoul
State/Province
Korea
ZIP/Postal Code
06591
Country
Korea, Republic of
Facility Name
Novartis Investigative Site
City
Surquillo
State/Province
Lima
ZIP/Postal Code
34
Country
Peru
Facility Name
Novartis Investigative Site
City
Hospitalet de LLobregat
State/Province
Catalunya
ZIP/Postal Code
08907
Country
Spain
Facility Name
Novartis Investigative Site
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
Novartis Investigative Site
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland
Facility Name
Novartis Investigative Site
City
Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Novartis Investigative Site
City
Balcova / Izmir
ZIP/Postal Code
35340
Country
Turkey
Facility Name
Novartis Investigative Site
City
Aberdeen
State/Province
Scotland
ZIP/Postal Code
AB25 2ZN
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Leeds
State/Province
West Yorkshire
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Liverpool
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom

12. IPD Sharing Statement

Links:
URL
http://NovartisClinicalTrials.com
Description
Related Info

Learn more about this trial

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

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