Inclusion Criteria:

1. Male or female patients aged ≥ 18 years old 2. Diagnosis of MM following at least one
prior therapy; there is no maximum number or prior therapies 3. Patients must have
relapsed/ refractory disease and be in need of therapy with evidence of measurable disease
defined as at least one of the following:

1. Serum M protein ≥ 0.5 g/dl (≥5g/l)

2. Urine M protein ≥ 200 mg/24 hours

3. Serum FLC assay: Involved FLC assay ≥ 10 mg/dl (≥100 mg/l) and an abnormal serum free
light chain ratio (< 0.26 or > 1.65)

4. Measurable plasmacytoma (Prior biopsy is acceptable) 4. Ability to provide written
informed consent obtained prior to participation in the study and any related
procedures being performed 5. Patients must meet the following laboratory criteria:

- ANC ≥ 1.0 x 109/L (growth factors cannot be used within 3 days of screening)

- Hemoglobin ≥ 8 g/dl (PRBC transfusions cannot be used within 3 days of
screening)

- Platelets ≥ 75x 109/L (platelet transfusions cannot be used within 3 days of
screening)

- AST and ALT ≤ 2.5 x ULN

- Serum bilirubin 1.5 x ULN

- Serum potassium ≥ LLN

- Total serum calcium [corrected for serum albumin] or ionized calcium ≥LLN.
(treatment of hypercalcemia is allowed and subjects may enroll if hypercalcemia
returns to normal with standard treatment)

- Serum magnesium ≥ LLN

- Serum phosphorus ≥ LLN

- Creatinine clearance ≥ 30 ml/min (Crockcroft-Gault calculation)

- Clinically euthyroid. Note: Patients are permitted to receive thyroid hormone
supplements to treat underlying hypothyroidism.

6. Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the
institutional normal.

7. ECOG Performance Status of ≤ 2 8. Must be willing and able to undergo bone
marrow aspirates per protocol (with or without bone marrow biopsy per
institutional guidelines). The bone marrow aspirate/biopsy must be adequate to
allow for comparison for the on-study efficacy assessments.

9. Females of childbearing potential (FCBP - A female of childbearing potential
is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral
oophorectomy; or 2) has not been naturally postmenopausal for at least 24
consecutive months. Confirmation that the subject is not pregnant must be
established by a negative serum -human chorionic gonadotropin (-hCG) pregnancy
test result obtained during screening. Pregnancy testing is not required for
post-menopausal or surgically sterilized women. FCBP must also agree to ongoing
pregnancy testing. Men must agree to use a latex condom during sexual contact
with a FCBP even if they have had a successful vasectomy.

Exclusion Criteria:

1. Prior HDAC, DAC, or valproic acid for the treatment of cancer 2. Prior treatment
with carfilzomib 3. Daily requirement for corticosteroids > prednisone 10 mg /day or
equivalent 4. Patients who will need valproic acid for any medical condition during
the study or within 5 days prior to first panobinostat treatment 5. 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 the Principal
Investigator prior to enrollment)

• History of congenital long QT syndrome

• Any history of ventricular fibrillation or torsade de pointes

• Bradycardia defined as HR< 50 bpm. Patients with pacemakers are eligible if HR ≥ 50
bpm.

• ECG evidence of acute ischemia or grade 3 conduction system abnormalities. (unless
subject has a pacemaker)

- Screening ECG with a QTc > 450 msec (read by local cardiologist)

- Right bundle branch block + left anterior hemiblock (bifascicular block)

- Patients with myocardial infarction or unstable angina ≤ 6 months prior to
starting study drug

- Other clinically significant heart disease (e.g., CHF NY Heart Association class
III or IV , uncontrolled hypertension, history of labile hypertension, or
history of poor compliance with an antihypertensive regimen) (Patients with a
history of atrial arrhythmias may be eligible if they are controlled and
approved by the Lead Principal Investigator) 4. Impairment of GI function or GI
disease that may significantly alter the absorption of panobinostat. Inability
to take oral medications, requirement for IV alimentation, active peptic ulcer
disease or prior surgical procedures or bowel resection affecting absorption of
oral medications.

5. Patients with diarrhea > CTCAE grade 1 (increase of 4 stools per day over
baseline mild increase in ostomy output compared to baseline).

6. 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.

7. Patients 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 [allow 72 hour
washout period]. (see Appendix I-table 1-1) 8. Concomitant use of CYP3A4
inhibitors (see Appendix I-table 2-1) 9. Patients who have received either
vaccine or antibody based therapy within < 8 weeks; chemotherapy within < 4
weeks, IMiDs within 2 weeks; or 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.

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

11. Peripheral blood stem cell transplant within 12 weeks of first dose of study
treatment.

12. Women who are pregnant or breast feeding or women of childbearing potential
(WOCBP) not using an effective method of birth control.

13. Male patients whose sexual partners are FCBP not using effective birth
control.

14. Patients with a prior malignancy with in the last 3 years (except for basal
or squamous cell carcinoma, or in situ cancer or low risk prostate cancer after
curative therapy or with > 90% remission at 5 years).

15. Patients with known positivity for human immunodeficiency virus (HIV) or
hepatitis C; baseline testing for HIV and hepatitis C is not required.

16. Patients with 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.

17. Significant neuropathy (≥ grade 3 or grade 2 with pain) within 14 days of
initiation of therapy.

18. Subjects with evidence of mucosal or internal bleeding, an active bleeding
diathesis and or known platelet transfusion refractoriness.

19. Patients with contraindications to any of the required concomitant drugs or
supportive treatments, including hypersensitivity to anticoagulation and
antiplatelet options, antiviral drugs, or tolerance to hydration due to
pre-existing pulmonary of cardiac impairment.

20. Patients with hypersensitivity to any of the components of the drug
including allergy to Captisol (a cyclodextrin derivative used to solubilize
carfilzomib), including voriconazole, ziprasidone, aripiprazole and amiodarone.

21. Ongoing graft-versus-host disease.