Phase I Study of LBH589, A Novel Oral Deacetylase Inhibitor in Patients With Recurrent or Refractory Hodgkin or Non-Hodgkin's Lymphoma

Inclusion Criteria:

- Male or female patients age ≥ 18 years old with relapsed/refractory Hodgkin lymphoma
or NHL patients who have relapsed or are refractory after receiving a minimum of two
prior therapies

- Ability to provide written informed consent obtained prior to participation in the
study and any related procedures being performed

Laboratory requirements:

- ANC ≥ 1.5 x 10(9th)/L, unless due to bone marrow involvement with lymphoma

- Hemoglobin ≥ 9 g/dl without packed red blood cell dependency, unless due to bone
marrow involvement with lymphoma

- Platelets ≥ 100 x 10(9th)/L, unless due to bone marrow involvement with lymphoma

- Serum creatinine ≤ 1.5 x Upper limit of Normal, or calculated Creatinine Clearance ≥
50 mL/min

- AST and ALT ≤ 2.5 x Upper limit of Normal, unless due to liver involvement with
lymphoma

- Serum bilirubin ≤ 1.5 x Upper limit of Normal

- Albumin > 3.0 g/dl

- Serum potassium ≥ Lower limit of Normal

- Total serum calcium [corrected for serum albumin] or ionized calcium ≥ Lower limits
of normal

- Serum magnesium ≥ Lower limit of Normal

- Serum phosphorus ≥ Lower limit of Normal

- TSH ≥ LLN and free T4 within normal limits. Patients are permitted to receive thyroid
hormone supplements to treat underlying hypothyroidism.

- Baseline MUGA or ECHO must demonstrate LVEF ≥ 50%

- ECOG Performance Status of ≤ 2

Exclusion Criteria:

- Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer

- Patients who will need valproic acid for any medication during the study or within 5
days prior to first LBH589 treatment

- Peripheral neuropathy ≥ CTCAE grade 1

- Impaired cardiac function or clinically significant cardiac diseases, including any
one of the following:

- Patients with congenital QT syndrome

- History or presence of sustained ventricular tachyarrhythmia.

- Any history of ventricular fibrillation or torsade de pointes

- Bradycardia defined as Heart Rate < 50 bpm. Patients with pacemakers are eligible if
Heart Rate ≥ 50 bpm

- Screening EKG with a QTc.450msec

- Right Bundle branch block + left anterior hemiblock (bifascicular block)

- Patients with myocardial infarction or unstable angina ≤ 6 months prior to starting
study drug

- other clinically significant heart disease (e.g. CHF NY Heart Association class III
or IV, uncontrolled hypertension, history of labile hypertension or history of poor
compliance with an antihypertensive regimen)

- Impairment of GI function or GI disease that may significantly alter the absorption
of LBH589

- Patients with Diarrhea > CTCAE grade 1

- Other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled
diabetes or active or uncontrolled infection) including abnormal laboratory values
that could cause unaccepted safety risks or compromise compliance with the protocol

- Patients using medications that have a relative risk of prolonging the QT interval or
inducing torsade de pointes if treatment cannot be discontinued or switched to a
different medication prior to starting study drug

- Concomitant use of CYP3A4 inhibitors

- Patients who have received targeted agents within 2 weeks or within 5 half-lives of
the agent and active metabolites(which ever is longer) and who have not recovered
from side effects of those therapies

- Patients who have received either immunotherapy within ≤ 8 weeks;chemotherapy within
≤ 4 weeks or radiation therapy to >30% of marrow-bearing bone within ≤ weeks prior to
starting study treatment or who have not yet recovered from side effects of such
therapies

- Patients with an active bleeding tendency or is receiving any treatment with
therapeutic doses of sodium warfarin or coumadin derivatives. Low doses of Coumadin
(e.g.≤2 mg/day) to maintain line patency is allowed.

- Patients who have undergone major surgery ≤ 4 weeks prior to starting study drug or
who have not recovered from side effects of such therapy

- Women who are pregnant or breast feeding or women of childbearing potential not using
effective method of birth control

- Male patients whose sexual partners are women of childbearing potential not using
effective birth control

- Patients with prior malignancy within 5 years (except for basal or squamous cell
carcinoma, in situ cancer of the cervix or early stage prostate or bladder
carcinomas)

- Patients with known positivity for HIV or hepatitis C: baseline testing for HIV and
Hepatitis C is not required

- Prior allogenic stem cell transplant

- Patients with any significant history of non-compliance to medical regimens or
unwilling or unable to comply with the instructions given to him/her by the study
staff

- Patients taking CYP2D6 inhibitors should be carefully monitored, but these drugs are
not necessarily contraindicated when use concomitantly with LBH. Use of these drugs
is not an exclusion criterion