Phase I/II Study of hLL1-DOX in Relapsed NHL and CLL

Inclusion Criteria:

Male or female, age ≥ 18 years
Able to provide signed, informed consent
Histologically confirmed diagnosis of recurrent B-cell non-Hodgkin's lymphoma (any histology by WHO criteria) or recurrent chronic lymphocytic leukemia (by NCI criteria) (Reference Appendix C)
Received at least one prior treatment with standard therapy (previous antibody therapy is acceptable)
Measurable disease at least one lesion ≥ 1.5 cm for NHL and ALC > 5,000 for CLL

Adequate performance status (≥ 70 Karnofsky scale) with an estimated life expectancy of at least 6 months

--Documented negative hepatitis B screen, per NCCN guidelines (hepatitis B surface antigen/antibodies, core antigen/antibodies, hepatitis B e-antigen)

At least 12 weeks beyond stem cell transplant and 4 weeks beyond chemotherapy or immunotherapy, major surgery, other experimental treatments, or radiation therapy to the index lesions, and with all acute toxicities from prior therapy resolved to less than Grade 2 toxicity by NCI CTC version 4.0
Laboratory parameters:

Adequate hematology without ongoing transfusional support Hemoglobin >/= 10 g/dL Absolute neutrophil count >/= 1.5 x 10 9/L Platelets >/= 75 x 10 9/L Creatinine and bilirubin
-Adequate cardiac function (MUGA scan or 2-D ECHO with LVEF ≥ 55%, EKG with no medically relevant arrhythmia uncontrolled on medications)

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
Prior treatment with trastuzumab
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
New York Heart Classification III or IV heart disease (see Appendix G). Other severe cardiovascular or cardiopulmonary disease, including COPD
Baseline BNP > 2 x IULN
Patients with uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities will be excluded
Patients with recent (≤ 6 months) cardiac angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrhythmias will be excluded
Known autoimmune disease or presence of autoimmune phenomena
At least 7 days beyond any infection requiring intravenous antibiotic use (Oral antibiotics may be administered prophylactically as clinically indicated)
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