Enrollment and/or interactions/interventions temporarily paused due to COVID-19 and expected to resume in the future. This is not a suspension of IRB approval.

This is a phase II study to evaluate the efficacy of ibrutinib in combination with bortezomib in in MCL (mantle cell lymphoma) patients who relapsed on single agent ibrutinib.

Inclusion Criteria:

• Men and women ≥ 18 years of age
• 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.
• Patients with history of MCL that has relapsed (documented disease progression after previously responding) to therapy (CR/PR) on single agent ibrutinib (treated for at least 6 months) as the last treatment prior to enrollment.
• Adequate liver, renal and bone marrow function
• Adequate coagulation (unless abnormalities are unrelated to coagulopathy or bleeding disorder)
• 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.)

Exclusion Criteria:

• Concurrent diagnosis of another malignancy unless treated with curative intent more than 2 years from study start (basal/squamous cell carcinoma of the skin is not an exclusion).
• Previous treatment with bortezomib.
• Patients who are eligible for autologous stem cell transplant are excluded unless they refuse this procedure.
• History of allogeneic stem cell transplant.
• Other exclusions (certain concurrent conditions) per protocol