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).

• Status: Completed
• Trial end date: 2019-04-29
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this randomized, two-arm, open-label expansion phase study was 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 also allowed collecting safety data of panobinostat in combination with 5-Aza in comparison to single-agent 5-aza.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Novartis Pharmaceuticals
• Treatments: Azacitidine; Panobinostat

Criteria

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 were 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 had 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 had evidence of clinically significant mucosal or internal bleeding