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

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

The purpose of this study is to find out the effects of a drug called LBH589 when given to people with recurrent or refractory Hodgkin or Non-Hodgkin's lymphoma. The safety of this drug will also be studied. The participants' physical state, changes in the size of the tumor, or state of Hodgkin or non-Hodgkin's Lymphoma, and laboratory findings taken while on-study will help the researchers decide if LBH589 is safe and effective.

This is an open-label, standard 3-3 dose finding scheme with a modification that allows intra-patient dose modification to determine maximum tolerated dose and toxicity profile of LBH589 in patients with recurrent or refractory Hodgkin's 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