Patient case: 1-year-old male with acute myeloid leukemia; genetic feature: IDH1

Clinical trial: 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).

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.


Eligibility: 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

Relevance to patient case: not relevant