A Phase Ib/IIb, Open-label, Multi-center, Study of Oral Panobinostat Administered With 5-Azacitidine (in Adult Patients With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML).
|Myelodysplastic Syndromes Chronic Myelomonocytic Leukemia Acute Myeloid Leukemia||Drug: Panobinostat (LBH589) and 5-Azacytidine Drug: 5-Azacytidine||Phase 1|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||A Phase Ib/IIb, Open-label, Multi-center, Study of Oral Panobinostat (LBH589) Administered With 5-Azacitidine (in Adult Patients With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML).|
- Incidence of dose limiting toxicity (DLT) (Phase l) [ Time Frame: 1 cycle (1 cycle = 28 days) ]D3, D5, D8, D10, D12, D15
- Composite Complete Response (CR) (CR or CRi or bone marrow CR) (Phase llb) [ Time Frame: 40 weeks ]By assessing preliminary efficacy of treatment with the panobinostat and 5-Aza combination at RPIID relative to treatment with single agent 5-Aza.
- Rate of partial and complete response (Phase l) [ Time Frame: After two, four and six LBH589 / Vidaza cycles (1 cycle 28 days) ]
- Clinical response for acute myeloid leukemia (AML) and for myeloid dysplastic syndromes(MDS)/chronic myelomonocytic leukemia (CMML) and Hematologic Improvement (HI) (Phase llb) [ Time Frame: 40 weeks ]AML, MDS, CMML: partial response (PR)
- Overall response (Phase llb) [ Time Frame: 40 weeks ]CR or CRi or bone marrow CR or PR
- 1-year survival rate (Phase llb) [ Time Frame: 40 weeks ]
- Time to progression (TTP) (Phase llb) [ Time Frame: 40 weeks ]Based on the Guidelines for Implementation of international working group (IWG) response criteria in AML, MDS and CMML according to Cheson 2003 and 2006 and specified in Post-text supplement 1.
- Type, duration, frequency and relatedness of Adverse Events (AE) (Phase llb) [ Time Frame: 40 weeks ]AE severity will be assessed according to NCI Common Terminology Criteria for Adverse Events (CTCAE), version 3.0
- Laboratory (Phase llb) [ Time Frame: 40 weeks ]biochemistry, hematology
- Electrocardiogram (ECG) monitoring (Phase llb) [ Time Frame: 40 weeks ]By central review using eRT
|Study Start Date:||December 2009|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2017 (Final data collection date for primary outcome measure)|
Experimental: Panobinostat + 5-Azacytidine
In phase I: Panobinostat : Escalating doses starting with 20 mg delivered orally at Day 3, Day 5, Day 8, Day 10, Day 12, Day 15.
In phase II: Panobinostat : Rapid Phase II doses at 30 mg delivered orally at Day 3, Day 5, Day 8, Day 10, Day 12, Day 15.
In both phases, dose of 5-Azacytidine will be 75 mg/m^2, subcutaneously Daily for Day 1 to Day 7.
Drug: Panobinostat (LBH589) and 5-Azacytidine
Each dose of panobinostat should be taken with 240 mL of water. Patients should be instructed to swallow the capsules whole and not chew them.
If the patient forgets to take his/her dose during the morning on a scheduled treatment day then the missed dose should be taken on that same day within 12 hours. After more than 12 hours, that day's dose should be withheld, and the patient should wait to take panobinostat until the next scheduled treatment day. The patient should then continue treatment with the original dosing schedule.
The days when panobinostat and 5-Aza are scheduled together (Day 3 and Day 5 of a treatment cycle), panobinostat should be administered approximately 30 min prior to 5-Aza.
Active Comparator: 5-Azacytidine
Dose of 5-Azacytidine : 75 mg/m^2 subcutaneously daily from Day 1 to Day 7.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00946647
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|Study Director:||Novartis Pharmaceuticals||Novartis Pharmaceuticals|