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

December 16, 2020 updated by: Novartis Pharmaceuticals

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

This study evaluated safety, tolerability, pharmacokinetics and preliminary anti-leukemic or anti-tumor activity of LBH589B in adult patients with advanced hematological malignancies

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

175

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Parkville, Victoria, Australia, 3002
        • Novartis Investigative Site
      • Prahran, Victoria, Australia, 3181
        • Novartis Investigative Site
  • Germany
      • Frankfurt/M, Germany, 60590
        • Novartis Investigative Site
      • Mainz, Germany, 55131
        • Novartis Investigative Site
  • United States
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Georgia Health Sciences University Dept.ofMedicalCollegeOfGeorgia
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana Farber Cancer Institute
    • Texas
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center/University of Texas

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Cycle 1 (28-day treatment cycle)
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.
Cycle 1 (28-day treamtent cycle)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
3.5 years
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.
1.2 years
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.
3.5 years
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.
3.5 years
Maximum Plasma Concentration of Panobinostat After the First Dose in Arms 1 and 2
Time Frame: Day 1
Day 1
Half Life of Panobinostat After the First Dose in Arms 1 and 2
Time Frame: Day 1
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
Day 15
Half Life of Panobinostat After Multiple Doses in Arm 1 on Day 15
Time Frame: Day 15
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.
Day 15/day 1
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.
Days 1, 5, 8, 10, 15
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)
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)
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)
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]))
Post dose to pre-dose (up to 3.5 years)
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]))
Post dose to pre-dose (up to 3.5 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Novartis Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2003

Primary Completion (Actual)

December 3, 2009

Study Completion (Actual)

December 3, 2009

Study Registration Dates

First Submitted

February 12, 2008

First Submitted That Met QC Criteria

February 21, 2008

First Posted (Estimate)

February 22, 2008

Study Record Updates

Last Update Posted (Actual)

January 5, 2021

Last Update Submitted That Met QC Criteria

December 16, 2020

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLBH589B2102
  • 2005-003670-26

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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