Efficacy and Safety of Panobinostat (LBH589) in Patients With Refractory de Novo or Secondary Acute Myelogenous Leukemia (AML)

Study Overview
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Brief Summary
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This study was to evaluate the efficacy and safety of single agent oral panobinostat in patients who have refractory de novo or refractory secondary AML.

Official Title
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A Phase II Study of Oral Single Agent Panobinostat in Patients With Refractory de Novo or Secondary Acute Myelogenous Leukemia (AML)

Conditions
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Refractory Leukemia, Acute Myelogenous Leukemia

Intervention / Treatment
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* Drug: Panobinostat/LBH589


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent prior to study-specific screening procedures Life expectancy of ≥ 60 days Eastern Cooperative Group (ECOG) performance status ≤ 2 Refractory AML with confirmed initial diagnosis of de novo AML (excluding APL) - OR- Refractory AML with confirmed initial diagnosis of AML (excluding APL) secondary to AHD or MDS with either condition precedent to AML (MDS/AHD) Negative serum pregnancy test (within 7 days of first dose) Negative urine pregnancy test immediately prior to first dose Exclusion Criteria: Known HIV Psychiatric disorder that interfered with ability to understand the study and give informed consent, and/or would impact study participation or follow-up Concurrent use of medications that might prolong the QT interval or of inducing Torsade de Pointes Female patients who were pregnant or breast-feeding or patients of childbearing potential who were not willing to use a double barrier method of contraception during the study and for 3 months following the last dose of study drug. Male patients whose sexual partner(s) were women of childbearing potential who were not willing to use a double method of contraception, one of which included a condom, during the study and for 3 months after the end of treatment Patient unable to swallow capsules Patients with impaired gastrointestinal systems which might cause interference with digesting and absorbing panobinostat Other Protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stratum A<br>patients with refractory acute myelogenous leukemia (AML) initially diagnosed as de novo AML received 60 mg of panobinostat per day on three discontinuous days per week. | Drug: Panobinostat/LBH589<br> <br> |
| Experimental: Stratum B<br>patients with refractory AML initially diagnosed as AML secondary to myelodysplastic syndrome (MDS)/antecedent hematologic disorder (AHD) received 60 mg of panobinostat per day on three discontinuous days per week. | Drug: Panobinostat/LBH589<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Response as Per Investigator Assessment by Stratum (FAS) | Response to treatment was defined as complete remission rate (CRR). CRR is complete remission (CR) and morphologic CR with incomplete blood count recovery (residual neutropenia or thrombocytopenia) (CRi). To stop or to proceed with Stage 2 of a given stratum of the Simon's optimal 2-stage design was based on the number of patients with CR/CRi and a safety evaluation of the patients from Stage 1 in that stratum. If early results clearly indicated that the drug was not active or worthy of further investigation, enrollment of that particular stratum would be terminated. CR and CRi were assessed by the Investigator according to IWG response Criteria for AML (Cheson et al 2003). As per protocol we would continue to stage II if ≥ 4 patients out of 26 patients enrolled to stage I had a CR or a CRi. As per response observed there was only 1 patient with CR/CRi in stratum A and 2 patients with CR/CRi in Stratum B. | 6 cycles of treatment with a 28-day treatment cycle (Day 168) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Partial Response Measured in Stratum A and B | As predefined in the study's protocol, stage II was not pursued due to lack of activity (at end of stage I less than 4 patients in each stratum with CR/CRi) | 6 treatment cycles (28-day/treatment cycle) | 
| Time to Remission Measured in Stratum A and B |  | 6 treatment cycles (28-day/treatment cycle) | 
| Duration of Remission Measured in Stratum A and B |  | 6 treatment cycles (28-day/treatment cycle) | 
| Event-free Survival Measured in Stratum A and B |  | 6 treatment cycles (28-day/treatment cycle) | 
| Overall Survival Measured in Stratum A and B |  | 6 treatment cycles (28-day/treatment cycle) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myeloid leukemia, AML, relapsed acute myeloid leukemia, refractory AML, refractory de novo AML, refractory secondary AML, secondary AML, AML following myelodysplastic syndrome (MDS), AML following antecedent hematological disorder (AHD), AML resistant to therapy