The Humanized Monoclonal Antibody Milatuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)
The Humanized Monoclonal Antibody Milatuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)
The purpose of this study is to determine whether Milatuzumab is effective in patients with
 refractory chronic lymphocytic leukemia, and also to find out in which range of doses is a
 response seen.
The aim of this study is to determine whether the anti-CD74 monoclonal antibody Milatuzumab
 provides benefit to subjects with CLL in advanced stage or progressive disease. The primary
 objectives of this study are to assess response rate to the agent, as well as the safety in
 CLL, using different doses: Overall response (OR), complete response (CR) and partial
 response (PR) will be determinate according to the NCI criteria.

 The secondary objectives are to determine: duration of response, time to progression, overall
 survival, and the range of doses in which efficacy is seen and MTD not reached.

 This study will be done in parallel with other phase I-II studies conducted by Immunomedics.

 The study design will take into account that the high levels of circulating CD74expressing
 cells in CLL may affect both the acute (although probably not long term) toxicity and the
 efficacy of the study medication. This could translate to a different MTD and a different
 cumulative dose of Milatuzumab, needed to achieve response.(either a higher dose or longer
 treatment period.).

 The study will be divided into two treatment phases. In the first phase we aim to address
 whether the dose of 120 mg/m2 is effective in CLL, and also if it is safe. In the second
 phase we will assess the safety and possible efficacy of higher doses, in those patients that
 did not achieve a significant response in the first phase. This will be done by gradual dose
 escalations, not to exceed 600 mg, or the MTD reached in other studies.

 In addition, the study will aim at gaining further understanding of the effect of Milatuzumab
 on the biological in-vitro function of CLL cells.
Inclusion Criteria:

 -  B-CLL confirmed according to NCI criteria

 -  CLL relapsed or refractory to prior antineoplastic therapy

 -  Signs of progressive disease; at least one:

 -  B symptoms

 -  lymphocyte doubling time of < 6 months

 -  symptomatic lymphadenopathy or splenomegaly

 -  cytopenias due to bone marrow failure)

 -  Age > 18 years, and less then 80

 -  Serum ALAT, ASAT, bilirubin, creatinine < 2x upper limit of normal

 -  Life expectancy > 6 months

 -  Patient's written informed consent

 Exclusion Criteria:

 -  Active bacterial or viral infection

 -  Hypersensitivity to humanized monoclonal antibodies

 -  Concurrent antineoplastic treatment for CLL or other malignant disease

 -  Absolute neutrophil count < 1.5 K/