Efficacy of Panobinostat in Patients With Relapsed and Bortezomib-refractory Multiple Myeloma

Inclusion Criteria

• Patient has a previous diagnosis of multiple myeloma, based on IMWG 2003 definitions. All three of the following criteria must have been met:
• Monoclonal immunoglobulin (M component) on electrophoresis, and on immunofixation on serum or on total 24 hour urine
• Bone marrow (clonal) plasma cells ≥ 10% or biopsy proven plasmacytoma
• Related organ or tissue impairment (CRAB symptoms: anemia, hypercalcemia, lytic bone lesions, renal insufficiency, hyperviscosity, amyloidosis or recurrent infections)
• Patient must have relapsed and refractory MM and must require treatment for the relapsed disease
• Patients must have received at least 2 prior lines of therapy which include an IMiD (thalidomide or lenalidomide)
• Patient must be refractory to the last bortezomib containing line of therapy given in the relapsed and refractory setting defined as:
• having progressed on or within 60 days of the last bortezomib-containing line of therapy
• Patient has measurable disease on M protein at study screening defined by at least one of the following measurements as per thresholds clarified in IMWG 2003 disease definitions (Kyle, et al 2003):
• Serum M-protein ≥ 1 g/dL (≥ 10 g/L)
• Urine M-protein ≥ 200 mg/24 h
• Patients treated with local radiotherapy with or without concomitant exposure to steroids for pain control or management of cord/nerve root compression, are eligible. Two weeks must have lapsed since last date of radiotherapy, which is recommended to be a limited field. Patients who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed and 2 weeks have passed since the last date of therapy
• Patient's age is ≥ 18 years at time of signing the informed consent
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤ 2
• Patient has the following laboratory values within 3 weeks before starting study drug (lab tests may be repeated, as clinically indicated, to obtain acceptable values before screen fail is concluded but supportive therapies are not to be administered within the week prior to screening tests for absolute neutrophil count or platelet counts)
• Absolute neutrophil count (ANC) ≥ 1.0 x 109 /L
• Platelet count ≥ 70 x 109 /L
• Serum potassium, magnesium, phosphorus, within normal limits (WNL) for institution
• Total calcium (corrected for serum albumin) or ionized calcium ≥ LLN, and not higher than CTCAE grade 1 in case of elevated value

Note: Potassium, calcium, magnesium, and/or phosphorus supplements may be given to correct values that are 450 msec on screening ECG

• Presence of unstable atrial fibrillation. Patients with stable atrial fibrillation are allowed in the study provided they do not meet other cardiac or prohibited drug exclusion criteria
• Previous history of angina pectoris or acute MI within 6 months
• Congestive heart failure (New York Heart Association functional classification III-IV)
• Patient has any other clinically significant cardiovascular disease (e.g. uncontrolled hypertension)
• Patient has an impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, malabsorption syndrome, obstruction, or significant small bowel resection)
• Patient has unresolved diarrhea ≥ CTCAE grade 2
• Patients who have any other concurrent severe and/or uncontrolled medical condition(s) including, but not limited to: uncontrolled diabetes mellitus, active or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease (e.g. dyspnea at rest from any cause), symptomatic thyroid dysfunction, significant bleeding tendency, that could cause unacceptable safety risks or compromise compliance with the protocol
• Patients who are using medications that have a known relative risk of prolonging the QT interval or of inducing Torsade de Pointes, where such treatment c