Atezolizumab (PD-L1 mAb) in Combination With Obinutuzumab and Ibrutinib in Patients With Relapsed Refractory or High-Risk Untreated Chronic Lymphocytic Leukemia (CLL)

Study Drug Administration:

Each study cycle is 28 days.

If participant is found to be eligible to take part in this study, participant will receive
obinutuzumab by vein over about 4-6 hours on Days 1, 2, 8, and 15 of Cycle 1 and then Day 1
of Cycles 2-9.

Participant will also receive atezolizumab by vein on Days 1 and 15 of Cycles 2-9. The first
time participant receives atezolizumab it should take about 1 hour. After that, if
participant tolerates the drug well, it may only take about 30 minutes to receive.
Participant will not receive atezolizumab during Cycle 1.

All participants will receive the same dose of obinutuzumab and atezolizumab.

If participant is already taking ibrutinib as part of participant's standard care,
participant will continue to take it at the current dose and schedule participant has been
assigned to by participant's regular doctor.

Study Visits:

On Days 1 and 15 of Cycles 1-9 and Days 8 and 22 of Cycle 2:

- Blood (about 1-2 teaspoons) will be drawn for routine tests. Part of this routine blood
draw may also be used for tests related to the immune system.

- Participant may have a physical exam.

On Days 2 and 8 of Cycle 1 and Days 8 and 22 of Cycles 3-6, blood (about 1-2 teaspoons) will
be drawn for routine tests.

On Day 15 of Cycle 1, participant may have these tests/procedures performed by participant's
local doctor, if it is closer to participant's home. During Cycle 2, all blood draws and
physical exams must be done at MD Anderson. After Cycle 2, participant must have physical
exams and blood draws performed at MD Anderson at least 1 time each month; all other exams
and draws can be done at participant's local clinic or doctor's office.

If blood draws and physical exams are done outside of MD Anderson, the results will be sent
to the study doctor for review.The option to have blood draws and physical exams at
participant's local doctor's office will be discussed with participant by the study doctor.

On Day 28 of Cycles 3, 6, and 9:

- Participant will have a physical exam.

- Blood (about 1-2 tablespoons) and urine will be collected for routine tests. These
routine tests will include a pregnancy test if participant can become pregnant.

- Participant will have a bone marrow biopsy/aspirate to check the status of the disease.

- Participant will have a CT or PET scan to check the status of the disease.

If the doctor thinks it is acceptable to do so, participant may skip the End of Cycle 3 visit
and have the Day 1 of Cycle 4 visit instead. This will be discussed with participant.

Length of Study:

Participant may continue receiving obinutuzumab and atezolizumab for up to 9 cycles. If
participant is receiving it, participant may continue to receive ibrutinib as part of
participant's standard care for as long as the doctor thinks it is in participant's best
interest. Participant will no longer be able to take the study drugs if the disease gets
worse, if intolerable side effects occur, or if participant is unable to follow study
directions.

Participation on the study will be over after about 1 year of follow-up visits.

End-of-Study Visit:

Within 30 days of participant's last dose of study drugs:

- Participant will have a physical exam.

- Blood (about 1-2 teaspoons) will be drawn for routine tests.

- If the doctor thinks it is needed, participant will have a bone marrow biopsy/aspirate
to check the status of the disease.

- If the doctor thinks it is needed, participant will have a CT or PET scan.

Long-Term Follow-Up:

After participant's end-of-study visit, participant will continue to have follow-up visits
for up to 1 year at the below time points.

One (1) time each month:

- Participant will have a physical exam.

- Blood (about 1-2 teaspoons) will be drawn for routine tests

Every 3-6 months:

- Participant will have a bone marrow biopsy/aspirate to check the status of the disease.

- Participant will have a CT or PET scan.

If participant starts a new type of anti-CLL treatment during the 1 year follow-up period,
participant will stop having these study visits.

This is an investigational study. Atezolizumab is not FDA approved or commercially available.
Its use in this study is investigational. Obinutuzumab and ibrutinib are FDA approved and
commercially available for use in the treatment of CLL. It is considered investigational to
use these drugs in combination with each other to treat CLL.

The study doctor can explain how the drugs are designed to work.

Up to 72 participants will be enrolled in this study. All will take part at MD Anderson.

Inclusion Criteria:

1. Patients will have a diagnosis of CLL or small lymphocytic lymphoma (SLL) who meet one
or more criteria for active disease as defined by the International Working Group for
CLL (IWCLL) and are: a) Cohort 1: refractory to or relapsed after at least one prior
therapy; or b) Cohort 2: untreated patients with high-risk molecular features such as
del(17p), mutated TP53, del(11q), unmutated IGHV gene, or are > 65 years of age; or
Cohort 3: Patients with CLL who have been on ibrutinib for at least 12 months with a
partial response

2. Age >/= 18 years

3. Eastern Cooperative Oncology Group (ECOG) Performance Status
4. Patients must have adequate renal and hepatic function: -- Serum bilirubin upper limit of normal (ULN). For patients with Gilbert's disease, serum bilirubin up
to 1.5 x ULN, -- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 3 x ULN

5. Females of childbearing potential must have a negative serum or urine beta human
chorionic gonadotrophin (Beta-hCG) pregnancy test result within 7 days prior to the
first dose of treatment and must agree to use an effective contraception method during
the study and for 6 months following the last dose of the study drugs. Females of non-
childbearing potential are those who are postmenopausal greater than 1 year or who
have had a bilateral tubal ligation or hysterectomy. Males who have partners of
childbearing potential must agree to use an effective contraceptive method during the
study and for 6 months following the last dose of study drugs.

6. Patients or their legally authorized representative must provide written informed
consent

Exclusion Criteria:

1. Prior malignancy active within the previous 2 years except for locally curable cancers
that have been apparently cured, such as basal or squamous cell skin cancer,
superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized
prostate cancer. If patients have another malignancy that was treated within the last
2 years, such patients may be enrolled if the likelihood of requiring systemic therapy
for this other malignancy within 2 years is less than 10%, as determined by an expert
in that particular malignancy at MD Anderson Cancer Center and after consultation with
the Principal Investigator.

2. Prior treatment for CLL with CTLA-4, PD-1, PD-L1, or CD137 mAb

3. Any major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy,
experimental therapy within 4 weeks prior to the first dose of the study drugs (except
ibrutinib for patients in Cohort 3). NOTE: for patients on oral targeted therapies
(such as ibrutinib, idelalisib, IPI-145, ACP-196), a wash-out of 3 days from cycle 1
day 1 is acceptable.

4. Adverse events from prior anticancer therapy that have not resolved to Grade except for alopecia

5. Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias,
congestive heart failure, or myocardial infarction within 2 months of screening, or
any Class 3 or 4 cardiac disease as defined by the New York Heart Association
Functional Classification

6. History of stroke or cerebral hemorrhage within 2 months

7. Patients who have uncontrolled hypertension (defined as sustained systolic blood
pressure >/= 160 mmHg or diastolic >/= 100 mmHg)

8. Known evidence of active cerebral/meningeal CLL. Patients may have a history of
central nervous system (CNS) leukemic involvement if definitively treated with prior
therapy and no evidence of active disease at the time of registration (defined as >/=
2 consecutive spinal fluid assessments with no evidence of disease)

9. Active, uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia requiring
steroid therapy

10. Patients with active autoimmune diseases are excluded: Patients with a history of
inflammatory bowel disease (including Crohn's disease and ulcerative colitis) are
excluded from this study as well as patients with a history of autoimmune disease
(e.g., rheumatoid arthritis, systemic progressive sclerosis, systemic lupus
erythematosus, Wegener's granulomatosis)

11. Patients with previous allogeneic stem cell transplant (SCT) are excluded within 6
months or with active acute or chronic graft-versus host disease are excluded.
Patients must be off immunosuppression for graft versus host disease (GVHD) for at
least 30 days before cycle 1 day

12. Patients with organ allografts (such as renal transplant) are excluded

13. Patients who are on high-dose steroids (doses >10mg/day of prednisone or equivalent)
or immune suppression medications. NOTE: Patients on high-dose steroids (doses
>10mg/day of prednisone or equivalent) or immune suppression medications are eligible
provided these drugs are discontinued at least 3 days prior to starting on the study
drugs

14. Patients with uncontrolled active infection (viral, bacterial, and fungal) are not
eligible

15. History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced),
organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing
pneumonia, etc.), or evidence of active pneumonitis on screening chest computed
tomography (CT) scan

16. Known clinically significant liver disease, including active viral, alcoholic, or
other hepatitis; cirrhosis; fatty liver; and inherited liver disease

17. Current or chronic hepatitis B or C infection, or known seropositivity for human
immunodeficiency virus (HIV)

18. Patient is pregnant or breast-feeding

19. Known hypersensitivity to Chinese hamster ovary cell products or other recombinant
human antibodies

20. Patients may not receive other concurrent investigational agent, chemotherapy,
radiotherapy, or immunotherapy for CLL. NOTE: Localized radiotherapy to an area not
compromising bone marrow function does not apply

21. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that in the opinion of the investigator may increase the risk associated
with study participation or investigational product administration or may interfere
with the interpretation of study results and/or would make the patient inappropriate
for enrollment into this study