Clinical trial NCT00621244: A Study of Oral LBH589 in Adult Patients With Advanced Hematological Malignancies
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lymphoma
Leukemia
Multiple Myeloma
Keywords: HDAC inhibitor
Oral
LBH589
Lymphoma
Leukemia
Multiple myeloma
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-02-22
Enrollment: 175
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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

Primary outcomes:
measure: Number of Participants DLT in Arm 1 in Dose Escalation Phase
timeFrame: Cycle 1 (28-day treatment cycle)
measure: Number of Participants DLT in Arm 2 in Dose Escalation Phase
timeFrame: Cycle 1 (28-day treamtent cycle)
Secondary outcomes:
measure: Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML)
timeFrame: 3.5 years
measure: Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML) in Expansion Phase
timeFrame: 1.2 years
measure: Response as Per Investigator Assessment for Patients With Hodgkin's Lymphoma (HD)
timeFrame: 3.5 years
measure: Response as Per Investigator Assessment for Patients With Myelodysplastic Syndromes (MDS)
timeFrame: 3.5 years
measure: Maximum Plasma Concentration of Panobinostat After the First Dose in Arms 1 and 2
timeFrame: Day 1
measure: Half Life of Panobinostat After the First Dose in Arms 1 and 2
timeFrame: Day 1
measure: Maximum Plasma Concentration of Panobinostat After Multiple Doses in Arm 1 on Day 15
timeFrame: Day 15
measure: Half Life of Panobinostat After Multiple Doses in Arm 1 on Day 15
timeFrame: Day 15
measure: Geometric Mean Ratio (GMR) Comparing Treatment Days in Arm 1
timeFrame: Day 15/day 1
measure: Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group X
timeFrame: Days 1, 5, 8, 10, 15
measure: Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group Y
timeFrame: Days 5, 8, end of study (up to 3.5 years)
measure: Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group X
timeFrame: Days 5, 8, 10, 12, 15, End of study, Unscheduled (up to 3.5 years)
measure: Percentage of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group Y
timeFrame: Days 5, 8, 10, 12, 15, End of study (up to 3.5 years)
measure: Highest Percent Change in Fetal Hemoglobin From Baseline in Arm 1 (MWF Every Week)
timeFrame: Post dose to pre-dose (up to 3.5 years)
measure: Highest Percent Change of Fetal Hemoglobin From Baseline in Arm 2 (MWF Every Other Week)
timeFrame: Post dose to pre-dose (up to 3.5 years)
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Georgia Health Sciences University Dept.ofMedicalCollegeOfGeorgia
state: Georgia
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Houston
country: United States
facility: MD Anderson Cancer Center/University of Texas
state: Texas
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Prahran
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Frankfurt/M
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: