Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

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Multiple Myeloma

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Lymphoma

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Neoplasms by Histologic Type

Lymphoproliferative Disorders

Immunoproliferative Disorders

Hematologic Diseases

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Panobinostat

Histone Deacetylase Inhibitors

Enzyme Inhibitors

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.

LBH589

Novartis Pharmaceuticals

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

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

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

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.

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.

Response as per investigator assessment for patients include complete response, progressive disease/failure, stable disease.

Response as per investigator assessment for patients include complete response, partial remission, stable disease, progressive disease (PD)/failure.

Response as per investigator assessment for patients include complete response, stable disease, progressive disease/failure, partial remission.

From day 15 by dose with schedule: MWF every week

MWF Every week schedule n = number of subjects with non-missing values.

Reporting the number of patients with a reading at the timepoint in the dose group.

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 \[96 hours\]))

Panobinostat was administered orally, once-a-day, on Monday-Wednesday-Friday (MWF), as part of a 28-day treatment cycle. Group X is a sub-arm, based on disease indication.

Arm1, Group X (20 mg)

Arm1, Group X (30 mg)

Arm1, Group X (40 mg)

Arm1 GroupX 60 mg

Arm1 GroupX 80 mg

Panobinostat was administered orally, once-a-day, on Monday- Wednesday-Friday (MWF), every week, as part of a 28-day treatment cycle. Group Y is a sub-arm, based on disease indication.

Arm1 GroupY 20 mg

Arm1 GroupY 30 mg

Arm1 GroupY 40 mg

Arm1 GroupY 60 mg

Arm2 GroupX 30 mg

Arm2 GroupX 45 mg

Arm2 GroupX 60 mg

Arm2 GroupX 80 mg

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.

Arm2 GroupY 30 mg

Arm2 GroupY 45 mg

Arm2 GroupY 60 mg

panobinostat was administered orally, once-a-day, on Monday-Wednesday-Friday (MWF), every week, as part of a 28-day treatment cycle. Group X indications (AML, CML-BC, AP, CP, ALL, MDS (RAEB-1, -2), MMM, CMML, aCML, CLL, and PLL) is a sub-arm, based on disease indication.

Arm 1, Group X

panobinostat was administered orally, once-a-day, on Monday-Wednesday-Friday (MWF), every week, as part of a 28-day treatment cycle. Group Y indications (MM, HL, and NHL) is a sub-arm, based on disease indication.

Arm 1, 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 X indications (AML, CML-BC, AP, CP, ALL, MDS (RAEB-1, -2), MMM, CMML, aCML, CLL, and PLL) is a sub-arm, based on disease indication.

Arm 2, Group X

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 indications (MM, HL, and NHL) is a sub-arm, based on disease indication.

Arm 2, Group Y

Total

Age, Continuous

Sex: Female, Male

Study Director

Arm 1, Group X (20 mg)

Arm 1, Group X (30 mg)

Arm 1, Group X (40 mg)

Panobinostat was administered orally, once-a-day, on Monday-Wednesday-Friday (MWF), as part of a 28-day treatment cycle. Groups X is a sub-arm, based on disease indication.

Arm 1, Group X (60 mg) - MTD

Arm 1, Group X (80 mg)

Panobinostat was administered orally, once-a-day, on Monday-Wednesday-Friday (MWF), as part of a 28-day treatment cycle. Group Y is a sub-arm, based on disease indication.

Arm 1, Group Y (20 mg)

Arm 1, Group Y (30 mg)

Arm 1, Group Y (40 mg) - MTD

Arm 1, Group Y (60 mg)

MTD-determining set: Patients in the safety set who were in the dose escalation phase, and who received panobinostat for ≥ 9 full doses in arm 1 in cycle 1 and completed all needed safety evaluations; or who received panobinostat for ≥ 5 full doses in arm 2 in cycle 1 and completed all required safety evaluations; or who experienced DLT in cycle 1.

Number of Participants DLT in Arm 1 in Dose Escalation Phase

Arm 2, Group X (30 mg)

Arm 2, Group X (45 mg)

Arm 2, Group X (60 mg)

Arm 2, Group X (80 mg)

Arm 2, Group Y (30 mg)

Arm 2, Group Y (45 mg)

Arm 2, Group Y (60 mg) - MTD

MTD-determining population: All patients from the safety population who were in the dose escalation phase of the study, and who received panobinostat for ≥ 9 full doses in arm 1 during cycle 1 and completed all required safety evaluations; or who received panobinostat.

Number of Participants DLT in Arm 2 in Dose Escalation Phase

Complete response (CR)

Partial remission (PR)

Stable disease (SD)

Progressive disease (PD)/failure

Not evaluable

Missing

Full Analysis Set: defined according to the Intention to Treat (ITT) principle. This population set included all patients to whom study treatment had been assigned.

Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML)

Full Analysis Set. Response as per investigator assessment for a subset of patients with AML accrued in the expansion phase (IA) include complete response, progressive disease/failure, stable disease.

Response as Per Investigator Assessment for Patients With Acute Myelogenous Leukemia (AML) in Expansion Phase

Response as Per Investigator Assessment for Patients With Hodgkin's Lymphoma (HD)

Response as Per Investigator Assessment for Patients With Myelodysplastic Syndromes (MDS)

Panobinostat was administered orally, once-a-day, on Monday-Wednesday-Friday (MWF)

20 mg

30 mg

40 mg

45 mg

60 mg

80 mg

Pharmacokinetic set: Pharmacokinetic population consisted of all patients who provided at least one postdose PK plasma sample.

Maximum Plasma Concentration of Panobinostat After the First Dose in Arms 1 and 2

Half Life of Panobinostat After the First Dose in Arms 1 and 2

Maximum Plasma Concentration of Panobinostat After Multiple Doses in Arm 1 on Day 15

Half Life of Panobinostat After Multiple Doses in Arm 1 on Day 15

C (max) N=8,12,18,17,4

Geometric Mean Ratio (GMR) Comparing Treatment Days in Arm 1

Day 1 (total=0, 1, 0, 0, 0)

Day 5 (total = 6, 4, 8, 17, 8)

Day 8 (total = 5, 4, 8, 17, 7)

Day 10 (total=0, 0, 0, 0, 0, 1)

Day 15 (total=3, 3, 4, 2, 2)

Arm 1, Group X (60 mg)

Full Analysis Set N=number of participants analyzed. total n=number of patients with a reading at the timepoint in the dose group.

Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group X

Day 5 (total= 1, 2, 15, 4)

Day 8 (total = 1, 3, 11, 4)

End of Study (total=1, 0, 0, 0)

Arm 1, Group Y (40 mg)

Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 1 (MWF Every Week), Group Y

Day 5 (total=4, 9, 6, 8)

Day 8 (total = 4, 7, 5, 7)

Day 10 (Total=3, 8, 5, 7)

Day 12 (Total=4, 6, 4, 8)

Day 15 (Total=4, 6, 2, 5)

End of Study (Total=1, 4, 2, 0)

Unscheduled (Total=2, 0, 0, 0)

Percentages of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group X

Day 5 (total=1, 4, 6)

Day 8 (total = 1, 4, 6)

Day 10 (total=1, 4, 5)

Day 12 (Total=0, 3, 5)

Day 15 (Total=1, 3, 5)

End of Study (Total=0, 2, 0)

Arm 2, Group Y (60 mg)

Percentage of Participants With Histone Acetylation Induction in Peripheral Blood in Arm 2 (MWF Every Other Week), Group Y

Panobinostat was administered orally, once-a-day, on Monday-Wednesday-Friday (MWF), every week.

Arm 1, Group x (30 mg)

Arm 1, Group Y (40mg)

Full Analysis Set (with available samples for analysis)

Highest Percent Change in Fetal Hemoglobin From Baseline in Arm 1 (MWF Every Week)

Panobinostat was administered orally, once-a-day, on Monday-Wednesday-Friday (MWF), every other week.

Highest Percent Change of Fetal Hemoglobin From Baseline in Arm 2 (MWF Every Other Week)

Overall Study

Spots Global Cancer Trial Database for A Study of Oral LBH589 in Adult Patients With Advanced Hematological Malignancies

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Study Description

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