Bortezomib in Combination With Ibrutinib in Ibrutinib Relapsed Mantle Cell Lymphoma

Inclusion Criteria:

- Adequate liver function

- Adequate renal function

- Adequate bone marrow function

- PT/INR <1.5 x ULN and PTT (aPTT) <1.5 x ULN

- Men and women ≥ 18 years of age

- Female subjects of childbearing potential must have a negative urine/serum pregnancy
test upon study entry. Women as well are not advised to breastfeed during treatment
with bortezomib and for 2 months after treatment.

- Male and female subjects of reproductive potential must agree to use both a highly
effective method of birth control and barrier method during the period of therapy and
for 30 days after the last dose of study drug for females and 90 days for males.

- Eastern Cooperative Oncology Group (ECOG) performance status of <2 (Eastern
Cooperative Oncology Group scoring system used to quantify general well-being and
activities of daily life; scores range from 0 to 5 where 0 represents perfect health
and 5 represents death.)

- Diagnosis of mantle cell lymphoma established by histologic assessment by a
hemato-pathologist with additional assessment of the histologic diagnosis by
immunohistochemistry or flow cytometry

- Adult patients with history of MCL that has relapsed (documented disease progression
after previously responding for at least 2 months to therapy (CR/PR) on single agent
ibrutinib as the last treatment prior to enrollment

Exclusion Criteria:

- Concurrent diagnosis of another malignancy unless treated with curative intent more
than 2 years from study start

- Previous treatment with bortezomib

- Allogeneic stem cell transplant patients are excluded

- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug

- Recent infection requiring systemic treatment that was completed ≤14 days before the
first dose of study drug

- Unresolved toxicities from prior anti-cancer therapy

- Known bleeding disorders (e.g., von Willebrand's disease or hemophilia)

- History of stroke or intracranial hemorrhage within 6 months prior to enrollment

- Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus
(HCV) or hepatitis B virus (HBV)

- Any uncontrolled active systemic infection

- Major surgery within 4 weeks of first dose of study drug