A Phase I Study Evaluating the Combination of the Deacetylase Inhibitor, LBH589 Plus the mTOR Inhibitor RAD001, in Relapsed and Refractory Adult Patients With Lymphoma

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