Study of the Combination of Panobinostat and Carfilzomib in Patients With Relapsed/Refractory Multiple Myeloma

Inclusion Criteria

• Eligible participants must have multiple myeloma using standard criteria.
• Patients must have measurable disease requiring systemic therapy defined as at least one of the following:
• Serum M-protein ≥1 g/dl (≥10 g/l)
• Urine M-protein ≥200 mg/24 hrs
• Serum free light chain assay: involved free light chain level ≥10 mg/dl (≥100 mg/l) provided the serum free light chain ratio is abnormal
• Must have progressed during or after at least one previous bortezomib-containing treatment regimen. Patients who have received previous high-dose therapy/autologous stem cell transplantation are eligible.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Must meet the following laboratory criteria:
• Absolute neutrophil count (ANC) ≥1000/μL;
• Platelets ≥70,000/microL;
• AST or ALT and alkaline phosphatase (ALP) must be ≤ 2.5 x ULN, or ≤ 5 x ULN in patients with plasmacytomas of the liver;
• Total bilirubin ≤ 1.5 x the institutional ULN;
• Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min;
• Serum potassium, calcium, magnesium WNL (These may be corrected prior to starting therapy, to make the patient eligible.)
• Ability to swallow oral medications.
• Baseline MUGA or ECHO must demonstrate left ventricular ejection fraction (LVEF) ≥ the lower limit of the institutional limits of normal.
• Male or females ≥ 18 years of age.
• Female patients must not be of child-bearing potential or must agree to use adequate contraceptive measures.
• Male patients willing to use adequate contraceptive measures.
• Willingness and ability to comply with the trial and follow-up procedures.
• Ability to understand the nature of this trial and give written informed consent.

Exclusion Criteria

• Currently receiving or have received systemic cancer therapy (chemotherapy, biologic therapy) ≤ 21 days of initiating study therapy. For patients receiving small molecule targeted therapy, study treatment may begin >21 days after last dose or >5 half lives of previous treatment, whichever is shorter. Patients must have completed radiation therapy ≥7 days prior to starting study treatment. Patients must have recovered from or come to a new chronic stable baseline from all treatment-related toxicities. Dexamethasone or other high-dose steroid therapy must be stopped ≥ days prior to starting study treatment.
• Previous treatment with HDAC, DAC, HSP90 or valproic acid for treatment of cancer.
• Requires valproic acid for any medical condition during the study ≤5 days prior to first panobinostat treatment.
• Patient has not recovered from all therapy-related toxicities associated with prior treatments to grade 2 diarrhea.
• Patients with impaired cardiac function.
• Infection requiring IV antibiotics.
• Patients with > grade 2 peripheral neuropathy or with uncontrolled pain.
• Women who are pregnant or lactating.
• Any concurrent medical illness that may impair the ability of the patient to tolerate study treatment and comply with the requirements of the study.
• Mental condition that would prevent patient comprehension of the nature of, and risk associated with, the study.
• Use of any non-approved or investigational agent ≤30 days prior to administration of the first dose of study drug. Patients may not receive any other investigational or anti-cancer treatments while participating in this study.
• Presence of other active cancers, or history of treatment for invasive cancer ≤ 5 years. Patients with stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.