Phase I/II Study of Different Doses and Dose Schedules of Milatuzumab (hLL1) in CLL

Milatuzumab (hLL1, IMMU-115), a humanized anti-CD74 monoclonal antibody. Dose escalation
will utilize 4 planned dose regimens with 4.0 or 8.0 mg/kg doses administered intravenously
either twice weekly (days 1 and 4) or thrice weekly (days 1, 3 and 5) for 4 consecutive
weeks. The four planned dose regimens will be labeled as dose level 1 to 4 corresponding to
increasing levels of the total dose of milatuzumab.

Inclusion Criteria:

- Histologically confirmed diagnosis of recurrent chronic lymphocytic leukemia (by NCI
criteria)

- Received at least one prior treatment with standard therapy (previous antibody
therapy is acceptable)

- Measurable disease (WBC > 5,000 for CLL)

- See protocol for full list

Exclusion Criteria:

- Pregnant or lactating women. Women of childbearing potential must have a negative
pregnancy test Pregnancy testing is not required for post-menopausal or surgically
sterilized women

- Women of childbearing potential and fertile men who are not practicing or who are
unwilling to practice birth control while enrolled in the study until at least 12
weeks after the last milatuzumab infusion

- Prior therapy with other human or humanized monoclonal antibodies, unless HAHA tested
and negative;

- Bulky disease by CT, defined as any single mass >10 cm in its greatest diameter

- Known HIV positive or active hepatitis B or C, or presence of hepatitis B surface
antigens or presence of hepatitis C antibody

- Known autoimmune disease or presence of autoimmune phenomena

- At least 7 days beyond any infection requiring antibiotic use.

- Systemic corticosteroids within 2 weeks, except low dose regimens (prednisone, <20
mg/day, or equivalent) which may continue if unchanged.

- Substance abuse or other concurrent medical or psychiatric conditions that, in the
Investigator's opinion, could confound study interpretation or affect the patient's
ability to tolerate or complete the study.