Obinutuzumab With High-dose Ibrutinib for the Treatment of Patients With Chronic Lymphocytic Leukemia With Progressive Disease on Single Agent Ibrutinib.

This is phase 1 study for patients with CLL or small lymphocytic lymphoma (SLL) experiencing
disease progression on single ibrutinib. This study will evaluate the optimal ibrutinib dose
(including doses higher than 420 mg) when combined with obinutuzumab.

During the screening period, patients will continue on ibrutinib at their previous tolerated
dose, unless required to stop (e.g.: by a preceding clinical trial).

On cycle 1, day 1, the dose of ibrutinib will be assigned based on the dose cohort. Patients
in cohort 1 will receive ibrutinib 420 mg PO daily. Patients in cohort 2 will receive
ibrutinib 560 mg PO daily. Cohort 3 will be 700 mg PO daily. Cohort 4 will be 840 mg PO
daily.

On cycle 1, day 1, patients will also initiate treatment with obinutuzumab (100 mg on day 1,
900mg on day 2, 1000mg day 8, 15, 28 then q 28 days for a total of 8 doses).

The primary safety endpoint is determination of DLTs during the first 28 days. The primary
efficacy endpoint of overall response rate will be assessed 2 months after the final dose of
obinutuzumab.

Inclusion Criteria:

- Clinical and phenotypic verification of B cell CLL or SLL and measurable disease.

- Prior therapy: Patients must have been receiving single agent ibrutinib therapy at the
time of disease progression. Patient may have received other therapy in combination
with ibrutinib earlier in the their treatment course. Prior obinutuzumab therapy is
also permitted.

- Progressive disease on current single agent ibrutinib therapy (but not within the
first 2 months of initiating ibrutinib therapy). Progression is based on 2008 iwCLL
definition.

- ECOG performance status of 0-2.

- Adequate hematologic function.

- Adequate renal function.

- Adequate hepatic function.

Exclusion Criteria:

- Known CNS lymphoma or leukemia

- History of Richter's or prolymphocytic transformation.

- Primary ibrutinib resistance, defined by progressive disease within the first 2 months
of first initiating ibrutinib therapy.

- Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura
(ITP)

- CLL therapy, with the exception of ibrutinib within the following timeframes:

1. Chemotherapy, external beam radiation therapy, anticancer antibodies within 30
days prior to the first dose of drug on this study.

2. Corticosteroid use 20mg prednisone within 1 week prior to first dose on this
study.

3. Radio- or toxin-conjugated antibody therapy within 10 weeks prior to first dose
on this study.

4. Allogeneic stem cell transplant within 6 months prior to first dose on this study

- History of major surgery within 4 weeks prior to first dose on this study.

- History of prior malignancy, with the exception of adequately treated non-melanoma
skin cancer, malignancies treated with curative intent and with no evidence of active
disease for more than 3 years, or adequately treated cervical carcinoma in situ
without current evidence of disease.

- Currently active clinically significant cardiovascular disease or history of
myocardial infarction within 6 months of first dose.

- Serologic status and/or PCR testing reflecting active hepatitis B or C infection.

- Known history of infection with human immunodeficiency virus (HIV).

- Unable to swallow capsules or disease significantly affecting gastrointestinal
function.

- History of stroke or intracranial hemorrhage within 6 months of first dose.

- Requires anticoagulation with warfarin or other Vitamin K antagonists.

- Requires treatment with a strong CYP 3A inhibitor.

- Pregnant or breast-feeding women

- Women of child-bearing age must obtain a pregnancy test and pregnant or breast feeding
females

- Patients who are currently receiving another investigational therapy

- Current infection requiring parenteral antibiotics.