A phase Ib/IIb, open-label, multi-center study of oral Panobinostat (LBH589) administered with 5-Azacitidine (Vidaza®) in adult patients with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) or acute myeloid leukemia (AML)
The goal of this clinical research study is to find the highest tolerable dose of panobinostat that can be given in combination with Vidaza® (azacitidine) to patients with MDS, CMML, or AML. The safety of this drug combination will also be studied.
Treatment Location: N/A
Phase Ib part Primary objectives To determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RPIID) of oral panobinostat in combination with a fixed dose of 5-Azacitidine (5-Aza) in adult patients with International Prognostic Scoring System (IPSS) intermediate-2 (INT-2) or high risk MDS, CMML, or AML. End-points for primary objectives Incidence of dose limiting toxicity (DLT) To determine the pharmacokinetic characteristics of the combination of oral panobinostat in combination with 5-azacitidine. Secondary objectives To characterize the safety and tolerability of panobinostat in combination with 5-Aza in the target patients population. End-points for secondary objectives Type, duration, frequency and relatedness of Adverse Events (AE). AE severity will also be assessed according to NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 Laboratory (such as biochemistry, hematology) ECG monitoring (central review by eRT) Exploratory objectives To evaluate preliminary anti-leukemic activity of panobinostat in combination with 5-Aza in terms of response, according to International Working Group (IWG) response criteria in AML and MDS To assess the effect of combined study treatment on gene expression and methylation status of specific genes known or suspected to be relevant to MDS/CMML/AML. Endpoints for exploratory objectives Clinical response for AML: CR, CRi, PR for MDS/CMML: CR, bone marrow CR, PR, HI Changes in DNA methylation and changes in gene expression in peripheral blood cells before and during therapy Phase IIb part Primary objective To assess preliminary efficacy of treatment with the panobinostat and 5-Aza combination at the RPIID relative to treatment with single agent 5-Aza through the assessment of composite CR (CR or CRi or bone marrow CR). End-points Composite CR (CR or CRi or bone marrow CR) Secondary objectives To assess preliminary efficacy of treatment with the panobinostat and 5-Aza combination at the RPIID relative to treatment with single agent 5-Aza through the assessment of clinical responses other than the composite CR specified in the primary objective, 1 yr survival, and time to progression (TTP). To characterize the safety and tolerability of panobinostat at the MTD and/or RPIID in combination with 5-Aza, as well as, 5-Aza alone in the target patient population. End-points Clinical response for AML: PR for MDS/CMML: PR, HI Overall response (CR or CRi or bone marrow CR or PR) 1-yr survival rate TTP based on the Guidelines for Implementation of IWG response criteria in AML, MDS and CMML. Type, duration, frequency and relatedness of AEs. AE severity will be assessed according to CTCAE, version 3.0 Laboratory (biochemistry, hematology) ECG monitoring (central review by eRT) Exploratory objectives To assess gene mutation status of specific target genes known to be relevant to MDS/CMML/AML disease. End-points Mutation status of genes known to be related to MDS/CMML/AML disease.
IRB Review and Approval Date: 05/27/2010
Recruitment Status: Closed
Projected Accrual: N/A
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