Study Of The Effectiveness & Safety Of Lenalidomide Versus Chlorambucil As First Line Therapy For Elderly Patients With B-Cell CLL (The ORIGIN Trial)

After notification from the US Food and Drug Administration (FDA) on 12 July 2013, Celgene
agreed to discontinue the lenalidomide treatment for all patients due to an imbalance in the
number of deaths in patients treated with lenalidomide versus patients treated with
chlorambucil. No specific causality for this imbalance has been identified to date.
Investigators were instructed to immediately discontinue all participants from experimental
lenalidomide treatment and inform their patients accordingly. Participants on the
Chlorambucil arm may continue up to 12 months (13 cycles) with the last participant
completing in March 2014. All randomized participants will continue to be followed for
overall survival and secondary primary malignancies.

Inclusion Criteria:

1. Must sign an informed consent form.

2. Age ≥ 65 years

3. Must be able to adhere to the study visit schedule and other protocol requirements.

4. Must have a documented diagnosis of B-cell CLL.

5. Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2.

6. Must agree to follow pregnancy precautions as required by the protocol.

7. Must agree to receive counseling related to teratogenic and other risks of
lenalidomide.

8. Must agree not to donate blood or semen as defined by the protocol

Exclusion Criteria:

1. Prior treatment for B-cell CLL.

2. Any medical condition, that would prevent the subject from signing the informed
consent form.

3. Active infections requiring systemic antibiotics.

4. Systemic infection that has not resolved > 2 months prior to initiating lenalidomide

5. Pregnant or lactating females.

6. Participation in any clinical study or having taken any investigational therapy within
28 days.

7. Known presence of alcohol and/or drug abuse.

8. Central nervous system (CNS) involvement.

9. Prior history of malignancies, other than CLL, unless the subject has been free of the
disease for ≥3 years. Exceptions include the following:

- Basal cell carcinoma of the skin

- Squamous cell carcinoma of the skin

- Carcinoma in situ of the cervix

- Carcinoma in situ of the breast

- Incidental histologic finding of prostate cancer (TNM stage of T1a or T1b)

10. History of renal failure requiring dialysis.

11. Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) and/or Hepatitis C
Virus (HCV) infection.

12. Prior therapy with lenalidomide.

13. Evidence of TLS at screening

14. Presence of specific hematology and/or chemistry abnormalities

15. Uncontrolled hyperthyroidism or hypothyroidism

16. Venous thromboembolism within one year

17. ≥ Grade-2 neuropathy

18. Uncontrolled autoimmune hemolytic anemia or thrombocytopenia

19. Disease transformation [i.e. Richter's Syndrome (lymphomas) or prolymphocytic
leukemia]