Amendment A, dated before first subject first visit Protocol amendment A was issued before first subject first visit, so changes were incorporated into the initial final protocol before first subject first visit (on September 18, 2007).

Amendment B, dated April 1, 2008 Protocol amendment B was issued before the start of patient enrollment in Phase II, to provide clarity around the patient population, that the text refers to the adult B-CLL population.

Amendment C, dated September 12, 2008 Protocol amendment C was issued before the start of patient enrollment in Phase II, based on the per protocol interim analysis scheduled to occur after the last patient enrolled in cohort 4 completed the cycle 4 response assessments. The objective of the interim analysis was to identify a single dose to take forward into the phase II NHL patient population. Re-treatment was also introduced at this time, with details provided as applicable for this sub-population. Following a thorough review of all available clinical, laboratory and pharmacokinetic data the participating investigators agreed (on July 10, 2008) that it was not possible to choose a single dose of the study drug to take into phase II. No dose limiting toxicities had been observed at doses up to 2000 mg. Preliminary efficacy data also indicated activity across all dose levels administered to date. The reviewers advised that it would be valuable for the drug’s development to open the phase II part of the study exploring two doses. The two doses selected for NHL patients in the phase II part of the study were: • 1600mg iv infusion on Cycle 1, days 1 and 8, and 800mg iv infusion for on day 1 of Cycles 2 to 8 • 400mg iv infusion on Cycle 1, days 1 and 8 and 400mg on day 1 of Cycles 2 to 8 The investigators also recommended that the two doses selected for the phase II part of the study should be tested in two relapsed/refractory CD20+ NHL populations: • Indolent NHL (40 patients [20 patients 1600/800mg and 20 patients 400mg]) • Aggressive NHL (40 patients [20 patients 1600/800mg and 20 pts 400mg])

Amendment D, dated April 09, 2009 Protocol amendment D was issued after the start of patient enrollment in the study (April 09, 2009) and included a justification for the selected Phase II CLL dose. Updates were also made to the primary objective of this part of the study as well as the study design (addition of an extra infusion on Day 15 and agreement to proceed with a 1000 mg flat dose for Phase II CLL patients). This amendment also introduced opportunity for re-treatment if believed to be beneficial for a patient by investigator, and such a request was made.

Amendment E, dated December 20, 2011 Protocol amendment E was issued on December 20, 2011. The main purpose of the amendment was to clarify the definition of end-of-study. The end-of-study was now defined as “2 years after the last patient has entered re-treatment unless all patients have left the study prior to this point,” rather than “2 years after the last patient has been enrolled into the study, unless all patients have discontinued the study prior to this time- point.” The schedule of assessments and other related text were adapted according to this clarification. Patients who were re-treated were considered to have withdrawn from follow-up. Follow-up data for re-treated patients was presented in a separate, but affiliated Clinical Study Report.

AMENDMENT F, dated November 21, 2012 The protocol was further amended to address a request from France’s Agence Nationale de Sécurité Medicament (ANSM) on 17 October 2012 to provide guidance on the diagnosis, evaluation, and management of a potential case of progressive multifocal leukoencephalopathy (PML). This protocol version was the subject of a country-specific amendment and implemented only in France.