Induction Therapy for Multiple Myeloma With Carfilzomib, Lenalidomide,Dexamethasone,Panobinostat

Inclusion Criteria:

- Male or female patients aged ≥ 18 years old

- Ability to provide written informed consent obtained prior to participation in the
study and any related procedures being performed

- Symptomatic multiple myeloma (per IMWG diagnostic criteria) and no prior treatment
for multiple myeloma

- Measurable disease with at least 1 of the following assessed within 21 days prior to
Cycle 1 Day 1: a.) Serum M-protein ≥ 0.5 g/d;, b.) Urine M-protein ≥ 200 mg/24 hour;
c.) In potential participants without detectable serum or urine M-protein, serum free
light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal serum kappa
lambda ratio.

- Must meet the following laboratory criteria within 21 days prior to Cycle 1, day 1:
a.) Absolute neutrophil count (ANC) ≥ 1 x 10^9/L; b.) Hemoglobin ≥ 8 g/dl; c.)
Platelet count ≥ 75,000/mm^3 unless thrombocytopenia is due to marrow infiltration by
myeloma; d.) AST and ALT ≤ 2.5 x upper limit of normal (ULN); e.) Serum bilirubin ≤
1.5 x ULN; f.) Serum Creatinine clearance ≥ 50 ml/min.

- Baseline multiple uptake gated acquisition scan (MUGA) or echocardiogram (ECHO) must
demonstrate left ventricular ejection fraction (LVEF) ≥ 45%

- Females of childbearing potential (FCBP) must have a negative serum pregnancy test
within the 10 to 14 days prior to study drug administration and a negative urine
pregnancy test within the 24 hours prior to the first study drug administration and
males who are sexually active with FCBP must agree to use 2 highly effective
concomitant methods of contraception including a male condom during the study and for
90 days following the last dose of study treatment

Exclusion Criteria:

- Prior histone deacetylase (HDAC), deacetylase (DAC), HSP90 inhibitors or valproic
acid for the treatment of cancer

- Potential participants who will need valproic acid for any medical condition during
the study or within 5 days prior to first panobinostat treatment

- Impaired cardiac function or clinically significant cardiac diseases, including any
one of the following: History or presence of sustained ventricular tachyarrhythmia.
(Patients with a history of atrial arrhythmia are eligible but should be discussed
with principal investigator prior to enrollment); Any history of ventricular
fibrillation or torsade de pointes; Bradycardia defined as HR< 50 bpm. (Patients with
pacemakers are eligible if heart rate (HR) ≥ 50 bpm.); Screening ECG with a QTc > 450
msec; Right bundle branch block + left anterior hemiblock (bifascicular block);
Patients with myocardial infarction or unstable angina ≤ 12 months prior to starting
study drug; Other clinically significant heart disease (e.g., chronic heart failure
(CHF) New York Heart Association class III or IV, uncontrolled hypertension, history
of labile hypertension, or history of poor compliance with an antihypertensive
regimen).

- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of panobinostat

- Diarrhea > NCI common terminology criteria for adverse events (CTCAE) grade 2

- Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled
diabetes or active or uncontrolled infection) including abnormal laboratory values,
that could cause unacceptable safety risks or compromise compliance with the protocol

- Using medications that have a relative risk of prolonging the QT interval or inducing
torsade de pointes if treatment cannot be discontinued or switched to a different
medication prior to starting study drug

- Have received prior treatment for multiple myeloma excluding dexamethasone not to
exceed 160 mg total

- Have received radiation therapy to > 30% of marrow-bearing bone within < 2 weeks
prior to starting study treatment; or who have not yet recovered from side effects of
such therapies.

- Have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not
recovered from side effects of such therapy

- Women who are pregnant or breast feeding or women of childbearing potential (WOCBP)
not using an effective method of birth control. Women of childbearing potential must
have a negative serum pregnancy test within 24 hrs of receiving the first dose of
study medication.

- Males whose sexual partners are WOCBP not using effective birth control

- A prior malignancy with in the last 5 years (except for basal or squamous cell
carcinoma, or in situ cancer of the cervix)

- Known positivity for human immunodeficiency virus (HIV) ) or hepatitis C; baseline
testing for HIV and hepatitis C is not required

- Any significant history of non-compliance to medical regimens or unwilling or unable
to comply with the instructions given to him/her by the study staff.

- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and
skin changes)

- Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard
differential)

- Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize
carfilzomib)

- Contraindication to any of the required concomitant drugs or supportive treatments,
including hypersensitivity to antiviral drugs, or intolerance to hydration due to
preexisting pulmonary or cardiac impairment