Lenalidomide and GA101 in Relapsed Indolent Non-Hodgkin's Lymphoma

Study Groups:

If you are found to be eligible to take part in this study, you will be assigned to a study
group based on when you join this study. Three (3) groups of up to 6 participants will be
enrolled in the Phase 1 portion of the study. Up to 60 participants will be enrolled in Phase
2.

If you are enrolled in the Phase 1 portion, the dose of lenalidomide you receive will depend
on when you joined this study. The first group of participants will receive the lowest dose
level of lenalidomide. Each new group will receive a higher dose of lenalidomide than the
group before it, if no intolerable side effects were seen. This will continue until the
highest tolerable dose of lenalidomide is found.

If you are enrolled in the Phase 2 portion, you will receive lenalidomide at the highest dose
that was tolerated in the Phase I portion.

All participants will receive the same dose level of obinutuzumab.

Study Drug Administration:

Each cycle is 28 days. You will be given a drug diary to record your doses.

On Days 2-22 of Cycles 1-6, you will take lenalidomide by mouth at about the same time daily.
You should take it with a glass of water on either a full or an empty stomach. Do not break,
chew, or open the capsules.

If you miss a dose of lenalidomide, take it as soon as you remember on the same day. If you
miss taking your dose for the entire day, take your regular dose the next scheduled day. Do
not take double your regular dose to make up for a missed dose.

If you take more than the prescribed dose of lenalidomide, you should seek emergency medical
care if needed and contact the study staff right away.

You will receive obinutuzumab by vein on Days 1, 2, 8, 15, and 22 of Cycle 1 and Day 1 of
Cycles 2-6. The first infusion will last about 4 hours. If this is well-tolerated, the next
infusions will take about 4-5 hours.

If you have stable disease you will continue receiving obinutuzumab and lenalidomide for up
to 12 cycles.

There is no "rest period". Participants will move to the extended dosing schedule after Cycle
6, where dosing of obinutuzumab will be given every other cycle.

Extended Dosing:

If you are responding, you may begin taking obinutuzumab on Day 1 on every even cycle (Cycles
8, 10, 12 and so on). You may continue taking lenalidomide until Cycle 12.

Study Visits:

Some of the tests and procedures may be done up to 7 days before the timing listed below.

On Day 1 of each cycle and Days 8, 15, and 22 of Cycle 1:

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

- If you are able to become pregnant, you will have a blood (about 1½ tablespoons)
pregnancy test.

- On Day 1 only, you will have a complete physical exam.

If your doctor thinks is it needed, on Day 14 of Cycles 2-12, blood (about 2 tablespoons)
will be drawn for routine tests.

On Cycles 3, 6, 9, 12 and then every 4 months after that:

- You will have a CT or PET/CT to check the status of the disease.

- If your doctor thinks it is needed, you will have a bone marrow biopsy and aspiration to
check the status of the disease.

Length of Treatment:

You may continue taking the study drugs for up to 30 months. You will no longer be able to
take the study drugs if the disease gets worse, if intolerable side effects occur, or if you
are unable to follow study directions.

Your participation on the study will be over once you have completed the end-of-treatment and
follow-up visits.

End-of-Treatment Visit:

Within 28 days after your last dose of study drug:

- You will have a physical exam.

- You will have a CT and/or PET/CT to check the status of the disease.

- You will have a chest x-ray to check the status of the disease.

- If your doctor thinks it is needed you will have a bone marrow biopsy and aspiration to
check the status of the disease.

- Blood (about 2 ½ tablespoons) will be drawn for routine tests.

- If you are able to become pregnant, you will have a blood (about 1½ tablespoons)
pregnancy test.

Depending on the disease status, you many have other tests to help further check the status
of the disease. The exact tests needed would be up to your doctor. Your doctor will discuss
these with you.

Long-term Follow-up:

If you stopped taking the study drug because the disease got worse, your study doctor will
follow up with you to check you how you are doing every 3 months for 1 year, every 6 months
for the next year, and then every year after that. At each clinic visit:

- You will have a CT scan and/or PET/CT to check the status of the disease.

- You will have a physical exam.

Inclusion Criteria:

1. A diagnosis of small lymphocytic lymphoma, follicular lymphoma (grades 1-3a), or
marginal zone lymphoma.

2. Evidence of progression or lack of response following at least 1 prior treatment for
indolent lymphoma.

3. Able and willing to provide written informed consent and to comply with the study
protocol

4. Age >/= 18 years

5. Must have at least 1 node greater than 1.5cm in short axis diameter

6. • Adequate hematologic function (unless abnormalities are related to NHL), defined as
follows: †† - Hemoglobin >/= 9.0 g/dL - Absolute neutrophil count >/= 1.5 x 10v9/L -
Platelet count >/= 75 x 10v9/L - ANC < 1.5 x 10v9 /L or PLT count less than 100
x10v9/L if cytopenia is due to extensive bone marrow involvement of disease as
determined by the treating physician.

7. For men who are not surgically sterile, agreement to use a barrier method of
contraception for >/= 3 months after the last obinutuzumab dose. In addition, male
patients must agree to request that their partners use an additional method of
contraception, such as oral contraceptives, intrauterine device, barrier method of
contraception, or spermicidal jelly

8. For women of reproductive potential who are not surgically sterile, agreement to use
two adequate methods of contraception, such as oral contraceptives, intrauterine
device, or barrier method of contraception in conjunction with spermicidal jelly for
>/= 12 months after the last obinutuzumab dose

9. Females of childbearing potential (FCBP)* must have a negative serum pregnancy test
with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within
24 hours of prescribing lenalidomide and must either commit to continued abstinence
from heterosexual intercourse or begin TWO acceptable methods of birth control, one
highly effective method and one additional effective method AT THE SAME TIME, at least
4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing
pregnancy testing. Men must agree to use a latex condom during sexual contact with a
female of child bearing potential even if they have had a successful vasectomy. *A
female of childbearing potential is a sexually mature woman who: 1) has not undergone
a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal
for at least 24 consecutive months (i.e., has had menses at any time in the preceding
24 consecutive months).

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

11. For patients with bulky disease (tumors >5cm); must be able to take aspirin (81mg or
325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use
warfarin or low molecular weight heparin.

12. Females of reproductive potential must adhere to the scheduled pregnancy testing as
required in the Revlimid REMS® program. Able to take aspirin (81 or 325 mg) daily as
prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low
molecular weight heparin).

Exclusion Criteria:

1. Evidence ongoing transformation into aggressive NHL.

2. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy

3. Known hypersensitivity to thalidomide or lenalidomide.

4. Regular treatment with corticosteroids during the 4 weeks prior to the start of Cycle
1, unless administered for indications other than NHL at a dose equivalent to mg/day prednisone

5. History of prior malignancy within the last 5 years, with the exception of curatively
treated basal or squamous cell carcinoma of the skin and low-grade in situ carcinoma
of the cervix

6. Evidence or history of significant, uncontrolled concomitant diseases that could
affect compliance with the protocol or interpretation of results, including
significant cardiovascular disease (such as New York Heart Association Class III or IV
cardiac disease, severe arrhythmia, myocardial infarction within the previous 6
months, unstable arrhythmias, or unstable angina) or pulmonary disease (including
obstructive pulmonary disease and history of bronchospasm)

7. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
(excluding fungal infections of nail beds) or any major episode of infection requiring
treatment with IV antibiotics or hospitalization (relating to the completion of the
course of antibiotics, except if for tumor fever) within 4 weeks prior to the start of
Cycle 1 Patients with suspected active or latent tuberculosis (latent tuberculosis
needs to be confirmed by positive Interferon-gamma release assay)

8. Vaccination with live vaccines within 28 days prior to start of treatment

9. Any of the following abnormal laboratory values (unless any of these abnormalities are
due to underlying lymphoma): Creatinine > 1.5 times the upper limit of normal (ULN)
(unless creatinine clearance normal), or calculated creatinine clearance < 40 mL/min
(using Cockcroft-Gault formula); AST or ALT > 2.5 x ULN; Total bilirubin > 1.5 x ULN
(or > 3 x ULN for patients with documented Gilbert syndrome).

10. Any history of hepatitis B infection.

11. Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology
testing) Patients positive for HCV antibody are eligible only if PCR is negative for
HCV RNA

12. Known history of HIV seropositive status

13. Positive test results for human T-lymphotropic 1 (HTLV 1) virus HTLV testing is
required in patients from endemic countries (Japan, countries in the Caribbean basin,
South America, Central America, sub Saharan Africa, and Melanesia)

14. Pregnant or lactating

15. Eastern Cooperative Oncology Group (ECOG) performance status greater than 2

16. Participation in another clinical trial with drug intervention within 21 days prior to
start of Cycle 1 and during the study

17. Patients with SLL/CLL are excluded during the phase I portion of the study