Phase I Study of Panobinostat + Bortezomib for Relapsed and/or Refractory Mantle Cell Lymphoma (MCL)

This is a phase I single arm, open label, multi-center (3 participating sites) dose
escalation study of oral panobinostat administered Monday-Wednesday-Friday (MWF) weekly x 4
weeks, utilizing 3+3 dosing scheme (15, 20, 25 mg) in combination with a fixed dose of
bortezomib 1.3 mg/m2 administered as a short intravenous (IV) infusion of 3-5 seconds every
week x 4 weeks, representing one cycle. Each week, bortezomib will be administered IV prior
to the oral dose of panobinostat. There will be sub-investigators participating in this
study who will enroll at sub-sites.

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

- Patients must have adequate hematology/chemistry lab values

- Echocardiogram (ECHO) must demonstrate Left Ventricular Ejection Fraction (LVEF) ≥
50%.

- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2

- Patients with previously diagnosed MCL based on standard criteria and with at least
one and a maximum of 4 lines of therapy and currently requiring further treatment

- Prior therapy with autologous and allogeneic stem cell transplant is permissible.
Patients who have undergone an allogeneic transplant should have no evidence of
graft-versus-host disease (GVHD) and should not be on any immunosuppressive therapy.
Autologous and allogeneic transplant will be counted as one prior therapy.

- Patients previously treated with bortezomib will be included in the study

Exclusion Criteria:

- Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer

- Patients who will need valproic acid for any medical condition during the study or
within 5 days prior to first LBH589 treatment

- Peripheral neuropathy ≥ CTCAE grade 2 on clinical examination within 14 days of
randomization

- Impaired cardiac function or clinically significant cardiac diseases

- Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of LBH589

- Patients with diarrhea > 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

- 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

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

- 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.

- Patients who 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. WOCBP are defined as sexually mature
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 24hrs of receiving the first dose of study
medication.

- Male patients whose sexual partners are WOCBP not using effective birth control

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

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

- 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.

- Allergic reaction to bortezomib