Inclusion Criteria

Inclusion criteria:

1. Patients must have a diagnosis of active multiple myeloma according to the
International Myeloma Working Group criteria (IMWG., 2003), and be deemed by the
investigator as requiring treatment.

2. Patients must have received at least one prior line of therapy and includes patients
whose disease has relapsed as well as relapsed-refractory MM . (Durie et. al., 2006).
One prior line of therapy may consist of induction followed by autologous stem cell
transplantation.

3. Patients must be suitable (according to their local product information and
applicable health authority recommendations) for treatment with BTZ. Note: patients
previously treated with BTZ are eligible to participate in the trial.

4. Patients enrolled to dose expansion phase must have measurable M component at entry
according to the IMWG Criteria (Durie et al, 2006) including at least one of the
following:

- Serum M-protein by sPEP ≥ 1 g/dL (> 10g/l)

- For patients with IgA M-protein whose sPEP is not providing sufficiently precise
quantification due to confounded migration of M-protein with serum beta
globulins, a quantification by nephelometry / turbidometry is permitted and
must show serum M-protein ≥ 1 g/dL

- Urine M-protein by uPEP ≥ 200 mg/24 h

- Serum FLC assay: Involved FLC level ≥ 100 mg/L, provided serum FLC ratio is
abnormal. (abnormal if FLC ratio is <0.26 or >1.65 )

5. Adults ≥ 18 years old

6. ECOG Performance Status ≤ 2

7. Life expectancy > 12 weeks

8. Patients must have the following laboratory values:

- ANC ≥ 1.5 x 109/L

- Platelets ≥ 100x 109/L

- Calculated CrCl ≥ 30 mL/min (MDRD Formula)

- AST and ALT ≤ 2.5 x ULN

- Serum bilirubin ≤ 1.5 x ULN

- Serum potassium, magnesium, phosphorous, within normal limits (WNL) for
institution

- Total calcium (corrected for serum albumin) or ionized calcium equal to lower
normal limits for institution or greater (≥ LLN) but not higher than CTCAE grade
1

- Note: Potassium, calcium, magnesium, and/or phosphorous supplements may be given
to correct values that are < LLN.

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

10. All patients (dose-escalation and dose-expansion patients) must be willing to undergo
a mandatory bone marrow aspirate sampling at baseline (for cytology) and another
later in the study if the patient eventually goes on to experience a CR or PR. For
patients who join the study at the dose-expansion phase, they must also give consent
to have an extra volume of sample taken for exploratory biomarker testing.
Potential dose-expansion phase patients who do not consent for this biomarker sample
collection will not be eligible to participate in the trial (Note: One extra bone
aspirate sample at C2D1 is optional as per the protocol).

11. Able to sign informed consent and to comply with the protocol

12. Patient is able to swallow capsules

Exclusion criteria:

1. Prior exposure to a HDAC inhibitor compound used in the treatment of MM

2. Patients with Refractory MM (i.e. patients refractory to all prior therapies) who
under all prior previous lines of therapy have :

- either never reached a response better than SD

- or whose disease progressed from any best response while still under therapy

- or whose disease progressed within 60 days of last dose of therapy

3. Patients who have had prior allogeneic stem cell transplantation and show evidence of
active graft-versus-host disease or of graft-versus-host disease that requires
immunosuppressive therapy.

4. Patient has grade 1 peripheral neuropathy with pain or grade ≥ 2 peripheral
neuropathy on clinical examination within 14 days before first study treatment

5. Impaired cardiac function or clinically significant cardiac diseases, including any
one of the following:

- Patients with congenital long QT syndrome

- History or presence of sustained ventricular tachyarrhythmia. (Patients with a
history of atrial arrhythmia are eligible but should be discussed with the
Sponsor prior to enrollment)

- Any history of ventricular fibrillation or torsade de pointes

- Bradycardia defined as HR< 50 bpm. Patients with pacemakers are eligible if 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 ≤ 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)

6. Impairment of GI function or GI disease that may significantly alter the absorption
of PAN

7. Patient has unresolved diarrhea ≥ CTCAE grade 2

8. Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled
diabetes, active or uncontrolled infection, acute diffuse pulmonary disease,
pericardial disease, uncontrolled thyroid dysfunction ) including abnormal laboratory
values, that could cause unacceptable safety risks or compromise compliance with the
protocol

9. 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

10. Patients who need valproic acid for any medical condition during the study or within
5 days prior to the first PAN treatment.

11. Patients who have received targeted agents within 2 weeks or within 5 half-lives of
the agent and active metabolites (which ever is longer) and who have not recovered
from side effects of those therapies.

12. Patients who have received either immunotherapy within ≤ 8 weeks; chemotherapy within
≤ 4 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.

13. Patients who have received steroids (e.g. Dex) ≤ 2 weeks prior to starting study
treatment or who have not recovered from side effects of such therapy. Concomitant
therapy medications that include corticosteroids are allowed if patients receive < 10
mg of prednisone or equivalent as indicated for other medical conditions, or up to
100 mg of hydrocortisone as pre-medication for administration of certain medications
or blood products while enrolled in this study.

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

15. Women who are pregnant or breast feeding or women of childbearing potential
(WOCBP)not willing to use a double method of contraception during the study and for 3
months after treatment. One of these methods of contraception must be a barrier
method. WOCBP are defined as women who have not undergone a hysterectomy or who have
not been naturally postmenopausal for at least 12 consecutive months (i.e., who has
had menses any time in the preceding 12 consecutive months). Women of childbearing
potential must have a negative serum pregnancy test within 7 days of the first
administration of oral PAN

16. Male patients whose sexual partners are WOCBP not using a double method of
contraception during the study and for 3 months after treatment. One of these methods
of contraception must be a condom

17. Patients with a prior malignancy with in the last 3 years (except for basal or
squamous cell carcinoma, or in situ cancer of the cervix)

18. 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.

19. Patients who have shown intolerance to BTZ or to Dex or components of these drugs or
has any contraindication to one or the other drug, following locally applicable
prescribing information

Other protocol defined inclusion/exclusion criteria may apply