Lenalidomide and Obinutuzumab for Previously Untreated CLL

This is phase 1/2 study for patients with CLL or (SLL) who have not been previously treated.
The primary endpoint is to determine safety and tolerability of the regimen and determine
complete response (CR) to therapy. The secondary endpoints will assess the impact of
treatment on progression free and overall survival

Eligible patients will receive obinutuzumab for 6 x 28 day cycles. Patients will also receive
lenalidomide orally once daily on days 8-28 of each 28 day cycles. The starting dose for all
patients is 5 mg PO daily. At the start of each cycle, there is intra-patient dose-escalation
to a maximum of 25mg daily, as tolerated.

- Main Inclusion Criteria:

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

2. Prior therapy: no prior CLL therapy.

3. Patients must have progressive disease based on 2008 iwCLL definition with one of
the following:

- Symptomatic or progressive splenomegaly

- Symptomatic lymph nodes, nodal clusters, or progressive lymphadenopathy

- Progressive anemia (hemoglobin ≤ 11 g/dL)

- Progressive thrombocytopenia (platelets ≤ 100 x 109/L)

- Weight loss > 10% body weight over the preceding 6 month period

- Fatigue attributable to CLL

- Fever or night sweats for > 2 weeks without evidence of infection

- Progressive lymphocytosis with an increase of > 50% over a 2-month period or an
anticipated doubling time of less than 6 months.

- Able to take aspirin (81mg or 325mg) daily, warfarin, low molecular weight heparin, or
equivalent anticoagulation as prophylactic medication.

- All study participants must be registered into the mandatory Revlimid REMS program,
and be willing and able to comply with the requirements of REMS.

- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy
test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again
within 24 hours prior to starting Revlimid and must either commit to continued
abstinence from heterosexual intercourse or begin TWO acceptable methods of birth
control.

- Females of reproductive potential must adhere to the scheduled pregnancy testing as
required in the Revlimid REMS program.

- ECOG performance status of 0-2.

- Adequate hematologic function

- Adequate renal function

- Adequate hepatic function

Exclusion Criteria:

- Pregnant or breast-feeding women will not be entered on this study due to risks of
fetal and teratogenic adverse events as seen in animal/human studies. Women for
child-bearing age must obtain a pregnancy test and pregnant or breast feeding females
are excluded.

- Known hypersensitivity to thalidomide or lenalidomide (if applicable), including
development of erythema nodosum or a desquamating rash while taking thalidomide or
similar drugs.

- Deep vein thrombosis or superficial thrombophlebitis of any cause on current
anticoagulation therapy at the time of screening.

- Patients who are currently receiving another investigational agent are excluded.

- Current infection requiring parenteral antibiotics.

- Known seropositive for or active viral infection with human immunodeficiency virus
(HIV); or known active infection with hepatitis B virus (HBV) or hepatitis C virus
(HCV) based on detectable viral load. Patients who are seropositive because of
hepatitis B virus vaccine or passive immunization by intravenous immunoglobulin (IVIG)
are eligible.

- Active malignancy within the previous 2 years (other than completely resected
non-melanoma skin cancer or carcinoma in situ).

- Known central nervous system (CNS) involvement by malignancy.

- Untreated autoimmunity such as autoimmune hemolytic anemia, or immune
thrombocytopenia.

- Insufficient recovery from surgical-related trauma or wound healing.

- Impaired cardiac function