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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00621244
• Other study ID #: CLBH589B2102
• Secondary ID: 2005-003670-26
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 1, 2003
• Est. completion date: December 3, 2009

Study information

• Verified date: July 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 175
• Est. completion date: December 3, 2009
• Est. primary completion date: December 3, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Leukemia
• Lymphoma
• Multiple Myeloma

Intervention

Drug:
• LBH589

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Parkville	Victoria
Australia	Novartis Investigative Site	Prahran	Victoria
Germany	Novartis Investigative Site	Frankfurt/M
Germany	Novartis Investigative Site	Mainz
United States	Georgia Health Sciences University Dept.ofMedicalCollegeOfGeorgia	Augusta	Georgia
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	MD Anderson Cancer Center/University of Texas	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Cycle 1 (28-day treatment cycle)
Primary	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.	Cycle 1 (28-day treamtent cycle)
Secondary	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.	3.5 years
Secondary	Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML) in Expansion Phase	Stage 2 did not open for enrollment.	1.2 years
Secondary	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.	3.5 years
Secondary	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.	3.5 years
Secondary	Maximum Plasma Concentration of Panobinostat After the First Dose in Arms 1 and 2		Day 1
Secondary	Half Life of Panobinostat After the First Dose in Arms 1 and 2		Day 1
Secondary	Maximum Plasma Concentration of Panobinostat After Multiple Doses in Arm 1 on Day 15	From day 15 by dose with schedule: MWF every week	Day 15
Secondary	Half Life of Panobinostat After Multiple Doses in Arm 1 on Day 15		Day 15
Secondary	Geometric Mean Ratio (GMR) Comparing Treatment Days in Arm 1	MWF Every week schedule n = number of subjects with non-missing values.	Day 15/day 1
Secondary	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.	Days 1, 5, 8, 10, 15
Secondary	Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group Y		Days 5, 8, end of study (up to 3.5 years)
Secondary	Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group X		Days 5, 8, 10, 12, 15, End of study, Unscheduled (up to 3.5 years)
Secondary	Percentage of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group Y		Days 5, 8, 10, 12, 15, End of study (up to 3.5 years)
Secondary	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]))	Post dose to pre-dose (up to 3.5 years)
Secondary	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]))	Post dose to pre-dose (up to 3.5 years)

External Links

•   Results for CLBH589B2102 can be found on the Novartis Clinical Trial Results Website