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

Phase 1

Completed

• Conditions: Lymphoma; Leukemia; Multiple Myeloma
• Interventions: Drug: LBH589

• Registration Number: NCT00621244
• Lead Sponsor: Novartis Pharmaceuticals

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

Detailed Description

Not available

Study Timeline

• Study Start: 2003-03-01
• Study First Submitted: 2008-02-12
• Study First Submitted QC: 2008-02-21
• Study First Posted: 2008-02-22
• Primary Completion: 2009-12-03
• Study Completion: 2009-12-03
• Disposition First Submitted: 2012-05-01
• Disposition First Submitted QC: 2012-05-01
• Disposition First Posted: 2012-05-03
• Results First Submitted: 2016-10-24
• Status Verified: 2017-07
• Results First Submitted QC: 2017-07-17
• Results First Posted: 2017-08-17
• Last Update Submitted: 2020-12-16
• Last Update Posted: 2021-01-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 175

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm 1, Group X	LBH589	-
Arm 1, Group Y	LBH589	-
Arm 2, Group X	LBH589	-
Arm 2, Group Y	LBH589	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants DLT in Arm 1 in Dose Escalation Phase	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	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

Name	Time	Method
Half Life of Panobinostat After Multiple Doses in Arm 1 on Day 15	Day 15
Geometric Mean Ratio (GMR) Comparing Treatment Days in Arm 1	Day 15/day 1	MWF Every week schedule n = number of subjects with non-missing values.
Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML) in Expansion Phase	1.2 years	Stage 2 did not open for enrollment.
Response as Per Investigator Assessment for Patients With Myelodysplastic Syndromes (MDS)	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	Day 1
Maximum Plasma Concentration of Panobinostat After Multiple Doses in Arm 1 on Day 15	Day 15	From day 15 by dose with schedule: MWF every week
Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group X	Days 1, 5, 8, 10, 15	Reporting the number of patients with a reading at the timepoint in the dose group.
Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML)	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 Hodgkin's Lymphoma (HD)	3.5 years	Response as per investigator assessment for patients include complete response, partial remission, stable disease, progressive disease (PD)/failure.
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)
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)
Highest Percent Change in Fetal Hemoglobin From Baseline in Arm 1 (MWF Every Week)	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)	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 \[96 hours\]))
Half Life of Panobinostat After the First Dose in Arms 1 and 2	Day 1
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)

Trial Locations

Locations (4)

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

MD Anderson Cancer Center/University of Texas; 🇺🇸 Houston, Texas, United States

Novartis Investigative Site; 🇩🇪 Mainz, Germany

Georgia Health Sciences University Dept.ofMedicalCollegeOfGeorgia; 🇺🇸 Augusta, Georgia, United States