A Phase II Study of LBH589, a Novel Histone Deacetylase Inhibitor, in Relapsed and Refractory Adult Patients With Acute Leukemia (AL) or in Newly Diagnosed Patients Over the Age of 60

Inclusion Criteria

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