Panobinostat in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed acute myeloid leukemia or acute lymphoblastic leukemia (ALL)

  • Relapsed or refractory disease
• Patients with Philadelphia chromosome-positive (Ph+) ALL refractory to BCR/ABL inhibitors are eligible
• Patients who have relapsed after prior autologous or allogenic stem cell transplant are eligible
• No active CNS disease

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Serum albumin ≥ 3 g/dL
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5.0 times ULN if transaminase elevation is due to leukemic involvement)
• Bilirubin ≤ 1.5 times ULN
• Creatinine ≤ 1.5 times ULN or creatinine clearance ≥ 50 mL/min
• Potassium ≥ lower limit of normal (LLN)
• Phosphorous ≥ LLN
• Serum total calcium (corrected for serum albumin) or serum ionized calcium ≥ LLN
• Magnesium ≥ LLN
• Thyroid stimulating hormone and free T4 normal (thyroid hormone replacement therapy allowed)
• LVEF ≥ LLN by MUGA or ECHO

• No impaired cardiac function, including any of the following:

  • QTc > 450 msec
  • Congenital long QT syndrome
  • History of sustained ventricular tachycardia
  • History of ventricular fibrillation or torsades de pointes

  • Bradycardia (i.e., heart rate < 50 beats per minute)

    • Pacemaker allowed provided heart rate ≥ 50 beats per minute
  • Myocardial infarction or unstable angina within the past 6 months
  • New York Heart Association class III-IV congestive heart failure
  • Right bundle branch block and left anterior hemiblock (bifascicular block)
• No uncontrolled hypertension
• No unresolved diarrhea > CTCAE grade 1
• No impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception during and for 3 months after completion of study treatment
• No other primary malignancy within the past 5 years, other than curatively treated carcinoma in situ of the cervix or basal cell or squamous cell carcinoma of the skin
• No HIV or hepatitis C positivity
• No other concurrent severe and/or uncontrolled medical condition
• No significant history of non-compliance to medical regimens or inability to give reliable informed consent

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• Recovered from all prior therapy
• More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy
• More than 4 weeks since prior valproic acid
• No other prior treatment with a histone deacetylase inhibitor
• No concurrent medication that may cause QTc prolongation or induce torsades de pointes
• No concurrent CYP3A4 inhibitors
• No concurrent grapefruit, grapefruit juice, or Seville (sour) oranges
• No concurrent radiotherapy
• No other concurrent anticancer therapy or investigational therapy