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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00621244




Registration number
NCT00621244
Ethics application status
Date submitted
12/02/2008
Date registered
22/02/2008
Date last updated
17/08/2017

Titles & IDs
Public title
A Study of Oral LBH589 in Adult Patients With Advanced Hematological Malignancies
Scientific 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
Secondary ID [1] 0 0
2005-003670-26
Secondary ID [2] 0 0
CLBH589B2102
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma 0 0
Leukemia 0 0
Multiple Myeloma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - LBH589

Experimental: Arm 1, Group X -

Experimental: Arm 1, Group Y -

Experimental: Arm 2, Group X -

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.


Treatment: Drugs: LBH589


Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants DLT in Arm 1 in Dose Escalation Phase - 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.
Timepoint [1] 0 0
Cycle 1 (28-day treatment cycle)
Primary outcome [2] 0 0
Number of Participants DLT in Arm 2 in Dose Escalation Phase - 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.
Timepoint [2] 0 0
Cycle 1 (28-day treamtent cycle)
Secondary outcome [1] 0 0
Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML) - Response as per investigator assessment for patients include complete response, progressive disease/failure, stable disease.
Timepoint [1] 0 0
3.5 years
Secondary outcome [2] 0 0
Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML) in Expansion Phase - Stage 2 did not open for enrollment.
Timepoint [2] 0 0
1.2 years
Secondary outcome [3] 0 0
Response as Per Investigator Assessment for Patients With Hodgkin's Lymphoma (HD) - Response as per investigator assessment for patients include complete response, partial remission, stable disease, progressive disease (PD)/failure.
Timepoint [3] 0 0
3.5 years
Secondary outcome [4] 0 0
Response as Per Investigator Assessment for Patients With Myelodysplastic Syndromes (MDS) - Response as per investigator assessment for patients include complete response, stable disease, progressive disease/failure, partial remission.
Timepoint [4] 0 0
3.5 years
Secondary outcome [5] 0 0
Maximum Plasma Concentration of Panobinostat After the First Dose in Arms 1 and 2
Timepoint [5] 0 0
Day 1
Secondary outcome [6] 0 0
Half Life of Panobinostat After the First Dose in Arms 1 and 2
Timepoint [6] 0 0
Day 1
Secondary outcome [7] 0 0
Maximum Plasma Concentration of Panobinostat After Multiple Doses in Arm 1 on Day 15 - From day 15 by dose with schedule: MWF every week
Timepoint [7] 0 0
Day 15
Secondary outcome [8] 0 0
Half Life of Panobinostat After Multiple Doses in Arm 1 on Day 15
Timepoint [8] 0 0
Day 15
Secondary outcome [9] 0 0
Geometric Mean Ratio (GMR) Comparing Treatment Days in Arm 1 - MWF Every week schedule n = number of subjects with non-missing values.
Timepoint [9] 0 0
Day 15/day 1
Secondary outcome [10] 0 0
Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group X - Reporting the number of patients with a reading at the timepoint in the dose group.
Timepoint [10] 0 0
Days 1, 5, 8, 10, 15
Secondary outcome [11] 0 0
Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group Y
Timepoint [11] 0 0
Days 5, 8, end of study (up to 3.5 years)
Secondary outcome [12] 0 0
Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group X
Timepoint [12] 0 0
Days 5, 8, 10, 12, 15, End of study, Unscheduled (up to 3.5 years)
Secondary outcome [13] 0 0
Percentage of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group Y
Timepoint [13] 0 0
Days 5, 8, 10, 12, 15, End of study (up to 3.5 years)
Secondary outcome [14] 0 0
Highest Percent Change in Fetal Hemoglobin From Baseline in Arm 1 (MWF Every Week) - 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]))
Timepoint [14] 0 0
Post dose to pre-dose (up to 3.5 years)
Secondary outcome [15] 0 0
Highest Percent Change of Fetal Hemoglobin From Baseline in Arm 2 (MWF Every Other Week) - 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]))
Timepoint [15] 0 0
Post dose to pre-dose (up to 3.5 years)

Eligibility
Key inclusion 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Parkville
Recruitment hospital [2] 0 0
Novartis Investigative Site - Prahran
Recruitment postcode(s) [1] 0 0
3002 - Parkville
Recruitment postcode(s) [2] 0 0
3181 - Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Georgia
Country [2] 0 0
United States of America
State/province [2] 0 0
Massachusetts
Country [3] 0 0
United States of America
State/province [3] 0 0
Texas
Country [4] 0 0
Germany
State/province [4] 0 0
Frankfurt/M
Country [5] 0 0
Germany
State/province [5] 0 0
Mainz

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This study evaluated safety, tolerability, pharmacokinetics and preliminary anti-leukemic or
anti-tumor activity of LBH589B in adult patients with advanced hematological malignancies
Trial website
https://clinicaltrials.gov/show/NCT00621244
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications