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

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

Official Title
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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

Conditions
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Lymphoma, Leukemia, Multiple Myeloma

Intervention / Treatment
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* Drug: LBH589


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1, Group X<br> | Drug: LBH589<br> <br> |
| Experimental: Arm 1, Group Y<br> | Drug: LBH589<br> <br> |
| Experimental: Arm 2, Group X<br> | Drug: LBH589<br> <br> |
| Experimental: Arm 2, Group Y<br>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<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Maximum Plasma Concentration of Panobinostat After the First Dose in Arms 1 and 2 |  | Day 1 | 
| Half Life 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 | 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 |  | Day 15 | 
| 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 | 
| 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 | 
| 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) | 
| 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) | 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) | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HDAC inhibitor, Oral, LBH589, Lymphoma, Leukemia, Multiple myeloma