Overview

This trial is active, not recruiting.

Conditions myelodysplastic syndromes, chronic myelomonocytic leukemia, acute myeloid leukemia
Treatments panobinostat (lbh589) and 5-azacytidine, 5-azacytidine
Phase phase 2
Targets HDAC, HIF-1a, VEGF
Sponsor Novartis Pharmaceuticals
Start date December 2009
End date December 2016
Trial size 112 participants
Trial identifier NCT00946647, 2009-010548-32, CLBH589H2101

Summary

The purpose of this randomized, two-arm, open-label expansion phase study is to collect preliminary efficacy data of panobinostat at the recommended phase II dose (RPIID) level in combination with azacytidine (5-Aza) versus an active control arm 5-Aza alone. This randomized phase II part allows also collecting safety data of panobinostat in combination with 5-Aza in comparison to single-agent 5-aza.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
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)
Dose of 5-Azacytidine : 75 mg/m^2 subcutaneously daily from Day 1 to Day 7.
5-azacytidine

Primary Outcomes

Measure
Incidence of dose limiting toxicity (DLT) (Phase l)
time frame: 1 cycle (1 cycle = 28 days)
Composite Complete Response (CR) (CR or CRi or bone marrow CR) (Phase llb)
time frame: 40 weeks

Secondary Outcomes

Measure
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
Overall response (Phase llb)
time frame: 40 weeks
1-year survival rate (Phase llb)
time frame: 40 weeks
Time to progression (TTP) (Phase llb)
time frame: 40 weeks
Type, duration, frequency and relatedness of Adverse Events (AE) (Phase llb)
time frame: 40 weeks
Laboratory (Phase llb)
time frame: 40 weeks
Electrocardiogram (ECG) monitoring (Phase llb)
time frame: 40 weeks

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: Phase l: - Patients with cytopathologically confirmed diagnosis of AML according to WHO criteria, excluding acute promyelocytic leukemia who are eligible for Vidaza treatment - ECOG performance status greater less than or equal to 2 Phase ll: - Adult patients (age ≥ 18 years) who are candidates for treatment with 5-Aza and present with one of the following: - intermediate-2 or high-risk myelodysplastic syndromes according to the International Prognostic Scoring System (IPSS). OR - AML with multilineage dysplasia and maximum of 30% blasts (former RAEB-T according to FAB) OR - chronic myelomonocytic leukemia (CMML) - Patients must have the following laboratory values unless elevations are considered due to MDS or leukemia: AST/SGOT and/or ALT/SGPT ≤ 2.5 x ULN; serum creatinine ≤ 1.5 x ULN; serum bilirubin (total and direct) ≤ 2 x ULN; electrolyte panel within normal ranges (WNL) for the institution. Exclusion Criteria: Phase l: - Prior treatment with deacetylase inhibitors - Concurrent therapy with any other investigational agent Phase ll: - Planned hematopoietic stem-cell transplantation (HSCT) - Patients with therapy-related MDS - Patients with therapy-related AML and/or relapsed/refractory AML - Patients with impaired cardiac function including any of the following: - Complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular tachyarrhythmia, clinically significant resting bradycardia (<50 beats per minute), QTcF > 460 ms on screening ECG, or right bundle branch block + left anterior hemiblock (bifascicular block) - Presence of unstable atrial fibrillation (ventricular response rate >100 bpm). Patients with stable atrial fibrillation are eligible provided they do not meet the other cardiac exclusion criteria - Previous history of angina pectoris or acute MI within 6 months - Screening LVEF <45% by echocardiography or MUGA - Other clinically significant heart disease (e.g. uncontrolled hypertension or history of poor compliance with an antihypertensive regimen). - Any of concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study. For example: - Uncontrolled diabetes - Active or uncontrolled infection - Uncontrolled hypothyroidism - Acute or chronic liver or renal disease - Patient has evidence of clinically significant mucosal or internal bleeding Other protocol-defined inclusion/exclusion criteria may apply

Additional Information

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).
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Novartis.