Panobinostat and Everolimus in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma

Inclusion Criteria

• •DISEASE CHARACTERISTICS:
• •Histologically confirmed diagnosis of one of the following:
• •* Hodgkin or non-Hodgkin lymphoma (including small lymphocytic lymphoma \[SLL\])
• •* Any histology, including B, T, or NK/T cell allowed
• •* Multiple myeloma (MM)
• •Relapsed or refractory disease
• •* Patients with lymphoma must have relapsed after or be refractory to an upfront regimen (e.g., CHOP or ABVD) and a salvage regimen (e.g., ICE or ESHAP)
• •* Patients with SLL should have relapsed after a fludarabine-containing regimen
• •* Patients with MM must have progressed within 100 days after receiving a regimen containing bortezomib and either thalidomide or lenalidomide AND have a 25% increase in serum paraproteins, urinary light chains, or plasma cell number in the bone marrow
• •No active CNS disease
• •PATIENT CHARACTERISTICS:
• •ECOG performance status 0-2
• •ANC ≥ 1,500/mm³
• •Platelet count ≥ 75,000/mm³ (transfusion allowed in patients with biopsy-proven bone marrow involvement)
• •AST and ALT ≤ 2.5 times upper limit of normal (ULN) (≤ 5.0 times ULN if elevation due to leukemic involvement)
• •Serum bilirubin ≤ 1.5 times ULN
• •Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
• •Serum potassium normal
• •Serum phosphorous normal
• •Serum total calcium (corrected for serum albumin) or serum ionized calcium normal
• •Serum magnesium normal
• •TSH and free T4 normal (thyroid hormone replacement allowed)
• •Fasting serum cholesterol ≤ 300 mg/dL (or ≤ 7.75 mmol/L) AND fasting triglycerides ≤ 2.5 times ULN (elevated levels allowed provided an appropriate lipid-lowering medication has been initiated)
• •LVEF normal by MUGA or ECHO
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective double-method (including barrier method) contraception during and for 3 months after completion of study treatment
• •No impaired cardiac function, including any of the following:
• •* QTc \> 450 msec by screening ECG
• •* Congenital long QT syndrome
• •* History of sustained ventricular tachycardia
• •* History of ventricular fibrillation or torsades de pointes
• •* Bradycardia, defined as heart rate (HR) \< 50 beats/min (pacemaker allowed provided HR ≥ 50 beats/min)
• •* Myocardial infarction or unstable angina within the past 6 months
• •* NYHA 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 impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral agents (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• •No other concurrent severe or uncontrolled medical condition
• •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 known HIV or hepatitis C positivity
• •No significant history of non-compliance to medical regimens
• •No known hypersensitivity to everolimus, other rapamycins (e.g., sirolimus or temsirolimus), or their excipients
• •PRIOR CONCURRENT THERAPY:
• •See Disease Characteristics
• •Prior autologous or allogeneic stem cell transplantation allowed
• •More than 3 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) or radiotherapy and recovered
• •More than 1 week since prior and no concurrent immunization with live attenuated vaccines
• •More than 4 weeks since prior valproic acid
• •No other prior histone deacetylase inhibitors
• •No concurrent chronic systemic corticosteroids or another immunosuppressive agent, other than for control of itching (as in cutaneous T-cell lymphoma)
• •* Concurrent corticosteroids allowed provided patient has been on a stable dosage regimen for ≥ 2 weeks before study entry
• •* Topical or inhaled corticosteroids allowed
• •No concurrent drugs that may induce torsades de pointes
• •No concurrent CYP3A4 inhibitors
• •No concurrent radiotherapy or other anticancer therapy
• •No concurrent grapefruit, grapefruit juice, or seville (sour) oranges
• •No concurrent medications that may cause QTc prolongation
• •No other concurrent investigational therapy