Panobinostat in Treating Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia or Acute Myeloid Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma
Intervention: panobinostat; gene expression analysis; reverse transcriptase-polymerase chain reaction; laboratory biomarker analysis
Intervention description: 40 mg Monday, Wednesday and Friday of every week in a 28 day cycle; Day 1 and day 28 samples; Day 1 and day 28 samples; Day 1 and day 28 samples
Intervention MeSH terms: Panobinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia; recurrent adult acute lymphoblastic leukemia; recurrent adult acute myeloid leukemia

Summary:

      RATIONALE: Panobinostat may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth.

      PURPOSE: This phase II trial is studying the side effects of panobinostat and to see how well
      it works in treating patients with relapsed or refractory acute lymphoblastic leukemia or
      acute myeloid leukemia.
    

Eligibility 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