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A Study of Oral LBH589 in Adult Patients With Advanced Hematological Malignancies

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00621244
First Posted: February 22, 2008
Last Update Posted: August 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
  Purpose
This study evaluated safety, tolerability, pharmacokinetics and preliminary anti-leukemic or anti-tumor activity of LBH589B in adult patients with advanced hematological malignancies

Condition Intervention Phase
Lymphoma Leukemia Multiple Myeloma Drug: LBH589 Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IA/II, Two-arm, Multi-center, Open-label, Dose-escalation Study of LBH589 Administered Orally Via Different Dosing Schedules in Adult Patients With Advanced Hematological Malignancies

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Number of Participants DLT in Arm 1 in Dose Escalation Phase [ Time Frame: Cycle 1 (28-day treatment cycle) ]
    Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for consecutive dosing schedule (MWF weekly). A 3-parameter version of a Bayesian logistic regression model with overdose control (Babb, Rogatko, and Zacks 1998) was used during the dose escalation phase for dose level selection and determination of the MTD.

  • Number of Participants DLT in Arm 2 in Dose Escalation Phase [ Time Frame: Cycle 1 (28-day treamtent cycle) ]

    Maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) for intermittent dosing schedule (MWF weekly).

    A 3-parameter version of a Bayesian logistic regression model with overdose control (Babb, Rogatko, and Zacks 1998) was used during the dose escalation phase for dose level selection and determination of the MTD.



Secondary Outcome Measures:
  • Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML) [ Time Frame: 3.5 years ]
    Response as per investigator assessment for patients include complete response, progressive disease/failure, stable disease.

  • Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML) in Expansion Phase [ Time Frame: 1.2 years ]
    Stage 2 did not open for enrollment.

  • Response as Per Investigator Assessment for Patients With Hodgkin's Lymphoma (HD) [ Time Frame: 3.5 years ]
    Response as per investigator assessment for patients include complete response, partial remission, stable disease, progressive disease (PD)/failure.

  • Response as Per Investigator Assessment for Patients With Myelodysplastic Syndromes (MDS) [ Time Frame: 3.5 years ]
    Response as per investigator assessment for patients include complete response, stable disease, progressive disease/failure, partial remission.

  • Maximum Plasma Concentration of Panobinostat After the First Dose in Arms 1 and 2 [ Time Frame: Day 1 ]
  • Half Life of Panobinostat After the First Dose in Arms 1 and 2 [ Time Frame: Day 1 ]
  • Maximum Plasma Concentration of Panobinostat After Multiple Doses in Arm 1 on Day 15 [ Time Frame: Day 15 ]
    From day 15 by dose with schedule: MWF every week

  • Half Life of Panobinostat After Multiple Doses in Arm 1 on Day 15 [ Time Frame: Day 15 ]
  • Geometric Mean Ratio (GMR) Comparing Treatment Days in Arm 1 [ Time Frame: Day 15/day 1 ]
    MWF Every week schedule n = number of subjects with non-missing values.

  • Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group X [ Time Frame: Days 1, 5, 8, 10, 15 ]
    Reporting the number of patients with a reading at the timepoint in the dose group.

  • Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group Y [ Time Frame: Days 5, 8, end of study (up to 3.5 years) ]
  • Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group X [ Time Frame: Days 5, 8, 10, 12, 15, End of study, Unscheduled (up to 3.5 years) ]
  • Percentage of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group Y [ Time Frame: Days 5, 8, 10, 12, 15, End of study (up to 3.5 years) ]
  • Highest Percent Change in Fetal Hemoglobin From Baseline in Arm 1 (MWF Every Week) [ Time Frame: Post dose to pre-dose (up to 3.5 years) ]
    All blood samples were drawn immediately prior to each administration of LBH589 dose and at the end of treatment (≤ 7 days post last dose (preferably ≥ 4 days [96 hours]))

  • Highest Percent Change of Fetal Hemoglobin From Baseline in Arm 2 (MWF Every Other Week) [ Time Frame: Post dose to pre-dose (up to 3.5 years) ]
    All blood samples were drawn immediately prior to each administration of LBH589 dose and at the end of treatment (≤ 7 days post last dose (preferably ≥ 4 days [96 hours]))


Enrollment: 175
Actual Study Start Date: March 1, 2003
Study Completion Date: December 3, 2009
Primary Completion Date: December 3, 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1, Group X Drug: LBH589
Experimental: Arm 1, Group Y Drug: LBH589
Experimental: Arm 2, Group X Drug: LBH589
Experimental: Arm 2, Group Y
Panobinostat was administered orally, once-a-day, on Monday-Wednesday-Friday (MWF), every other week, as part of a 28-day treatment cycle. Group Y is a sub-arm, based on disease indication.
Drug: LBH589

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Adult patients (≥18 years old) with advanced hematological malignancies who relapsed after or are refractory to standard therapy, or for which no standard therapy existed; or, were considered inappropriate candidates for standard therapy
  • World Health Organization (WHO) performance status ≤ 2
  • Patients who met protocol-specified hematologic and non-hematologic laboratory values
  • Patients with adequate liver and renal function

Exclusion criteria:

  • Concurrent brain metastases or leukemic infiltration of the cerebrospinal fluid
  • Peripheral neuropathy ≥ CTCAE grade 2
  • Unresolved diarrhea ≥ CTCAE grade 2
  • Concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study, including impaired heart function or clinically significant heart disease, and impaired gastrointestinal function or disease that significantly altered aborption of LBH589
  • Female patients who were pregnant or breast feeding
  • Patients who were unwilling to use an effective method of birth control
  • Patients who took medications specified by the protocol as prohibited for administration in combination with LBH589
  • Patients with another primary malignancy that required active intervention or were clinically significant
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00621244


Locations
United States, Georgia
Georgia Health Sciences University Dept.ofMedicalCollegeOfGeorgia
Augusta, Georgia, United States, 30912
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Texas
MD Anderson Cancer Center/University of Texas
Houston, Texas, United States, 77030
Australia, Victoria
Novartis Investigative Site
Parkville, Victoria, Australia, 3002
Novartis Investigative Site
Prahran, Victoria, Australia, 3181
Germany
Novartis Investigative Site
Frankfurt/M, Germany, 60590
Novartis Investigative Site
Mainz, Germany, 55131
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00621244     History of Changes
Other Study ID Numbers: CLBH589B2102
2005-003670-26
First Submitted: February 12, 2008
First Posted: February 22, 2008
Results First Submitted: October 24, 2016
Results First Posted: August 17, 2017
Last Update Posted: August 17, 2017
Last Verified: July 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
HDAC inhibitor
Oral
LBH589
Lymphoma
Leukemia
Multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Panobinostat
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action