study of lbh589, a deacetylase inhibitor in patients with recurrent or refractory hodgkin or non-hodgkin's lymphoma

Conditions: Hodgkin's Lymphoma; Non-Hodgkin's Lymphoma

Summary: 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.

Eligibility criteria:
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

Keywords: recurrent refractory