AIM study: This phase II trial is assessing the combination of two drugs (ABT-199 and irutinib) for the treatment of Mantle Cell LymphomaA Phase 2 Study of ABT-199 in Combination With Ibrutinib in the Treatment of Patients With Relapsed or Refractory Mantle Cell Lymphoma (AIM Study)

Exclusion

1. Subject has undergone an allogeneic stem cell transplant within the last 6 months or currently has active graft-vs-host disease requiring the use of immunosuppressants.
2. Subject has active and uncontrolled autoimmune cytopenias (for 2 weeks), including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenic purpura (ITP).
3. Subject has known central nervous system involvement by MCL.
4. Subject previously participated in an ibrutinib clinical trial or subject previously received a Bruton's tyrosine kinase (BTK) inhibitor other than ibrutinib

5. Subject has received the following within 30 days prior to the first dose of study drug:

   •Monoclonal antibody given with anti-neoplastic intent.

6. Subject has received any of the following within 14 days prior to the first dose of study drug, or has not recovered to less than CTC grade 2 clinically significant adverse effect(s)/toxicity(s) of the previous therapy:

   • Any anti-cancer therapy including chemotherapy, or radiotherapy;
   • Investigational therapy, including targeted small molecule agents.

7. Subject has received the following within 7 days prior to the first dose of study drug:

   •Steroid therapy given with anti-neoplastic intent

8. Subjects requires ongoing therapy with:

   • Potent CYP3A inhibitors (such as indinavir, ketoconazole, and clarithromycin),
   • Potent CYP3A inducers (e.g., rifampin, phenytoin, carbamazepine or St. John's Wort),
   • Warfarin, or or equivalent vitamin K antagonist (eg, phenprocoumon),
   • Antiretroviral medications.

9. Subject has consumed the following within 3 days prior to the first dose of study drug.

   • Grapefruit, or
   • Grapefruit products, or
   • Seville oranges (including marmalade containing Seville oranges), or
   • Star fruit
10. Subject has clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.

11. Subject has a life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.

    •specifically, a subject with history of stroke or intracranial hemorrhage within 6 months prior to enrollment is excluded

12. Subject has a history of other active malignancies other than MCL within the past 2 years prior to study entry, with the exception of:

    • Adequately treated in situ carcinoma of the cervix uteri,
    • Adequately treated basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin,
    • Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
13. Subject has known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics.
14. Received live, attenuated vaccines within 4 weeks of first dose of ibrutinib
15. Major surgery within 4 weeks of first dose of ibrutinib