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.