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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

Phase 2
18 Years
Not Enrolling

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Trial Information

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



- To determine the antitumor activity of panobinostat, in terms of objective response
rate, time to progression, and survival, in patients with relapsed or refractory acute
lymphoblastic leukemia or acute myeloid leukemia.

- To assess the toxicity of panobinostat in these patients.


- To perform correlative laboratory studies to assess changes in various proteins that
may be altered by histone deacetylase inhibition therapy.

OUTLINE: Patients receive oral panobinostat once on days 1, 3, and 5. Treatment repeats
every 28 days for up to 6 courses in the absence of disease progression or unacceptable

Patients undergo peripheral blood and bone marrow sample collection at baseline and on day
28 of course 1 for correlative laboratory studies. Samples are analyzed by RT-PCR for
reactivation of FANCG, FOXO3A, GADD45A, GADD45B, GADD45G, H2AX, and TP73.

After completion of study treatment, patients are followed for at least 4 weeks.

PROJECTED ACCRUAL: A total of 74 patients (37 with acute myeloid leukemia and 37 with acute
lymphoblastic leukemia) will be accrued for this study.

Inclusion Criteria


- 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


- 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


- 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


- 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

- No concurrent CYP3A4 inhibitors

- No concurrent grapefruit, grapefruit juice, or Seville (sour) oranges

- No concurrent radiotherapy

- No other concurrent anticancer therapy or investigational therapy

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Hematological response rate (morphologic complete response or partial response)

Outcome Time Frame:

1 year after completion of treament

Safety Issue:


Principal Investigator

Leslie Popplewell, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

April 2008

Completion Date:

September 2010

Related Keywords:

  • Leukemia
  • Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia
  • recurrent adult acute lymphoblastic leukemia
  • recurrent adult acute myeloid leukemia
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



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South Pasadena Cancer Center South Pasadena, California  91030