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

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