Optimal Dose Finding Study ABT-199 and Ibrutinib in MCL

This is a multi-center, study which will be open at up to 4 clinical sites. The purpose of
this study is to determine the optimal dosing scheme for the combination of ibrutinib with
ABT-199 for the treatment of relapsed or refractory mantle cell lymphoma (MCL). The main
criterion for eligibility is MCL with measurable disease which is relapsed or refractory to
at least 1 chemotherapy-containing regimen and has not been previously treated with
ibrutinib.

This dose finding study will use a continual reassessment method, which accounts for both
toxicity and efficacy in combinations of agents, to determine the optimal combination of the
approved treatment ibrutinib with the investigational agent ABT-199. This study will accrue
patients in two stages. In the initial stage, subjects will be accrued to dosing cohorts of
increasing dosages of ABT-199 in combination with ibrutinib. The modeling is initiated once 1
subject experiences a dose limiting toxicity (DLT). During the modeling stage, treatment
assignments will be made based on model prediction.

Subjects will remain on treatment until progression or unacceptable toxicity, and will be
monitored for safety during the treatment interval. Safety will be evaluated by incidence of
adverse events and number of discontinuations due to AEs. Efficacy endpoints include Overall
Response Rate (ORR), Complete Response Rate (CRR), minimal residual disease response rate,
and survival (PFS and OS). The study will also include exploratory analysis of the gene
expression pattern in subjects who progress on treatment.

Inclusion Criteria:

1. Diagnosed with Mantle Cell Lymphoma and has had at least one chemotherapy.

2. Subjects must have measurable or evaluable disease.

3. ECOG Performance Status of 0-2.

4. Must be referred for treatment with ibrutinib.

5. Must have adequate organ function.

Exclusion Criteria:

1. Subject is pregnant.

2. Prior malignancy (except nonmelanomatous skin cancer) unless disease free for a
minimum of 2 years; non-invasive conditions such as carcinoma in situ of the breast,
oral cavity, or cervix are all permissible.

3. Known CNS lymphoma.

4. Prior or current treatment with certain medications. Talk to Study Contact for
specifics.

5. Subject is at high risk for TLS.

6. Subject has malabsorption syndrome or other condition which may affect an enteral
route of administration.

7. Subject has known contraindication or allergy to both xanthine oxidase inhibitors and
rasburicase.

8. Significant history of heart disease.

9. Subject has an active infection.

10. Known active Hepatitis B or Hepatitis C.

11. A serious uncontrolled medical disorder that in the opinion of the investigator would
impair the ability of the subject to receive protocol therapy.