A Phase II Trial of Alemtuzumab and Rituximab in Patients With Previously Untreated CLL

Response rate (complete remission(CR) + partial remission(PR)) will be, assessed by NCI-WG 1996 criteria with lymphadenopathy and organomegaly measured during physical examination. CR=Absence of lymphadenopathy and constitutional symptoms, Normal CBC (leukocytes ≥ 1500/μl, Platelets \>100,000/μl, Hemoglobin \> 11.0 gm/dl), peripheral blood lymphocytes ≤ 4,000/μl.The marrow sample must be at least normocellular with \< 30% of nucleated cells being lymphocytes. PR=absence of constitutional symptoms, ≥ 50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value, ≥ 50% reduction in lymphadenopathy, ≥ 50% reduction in size of liver and/or spleen and one of the following: polymorphonuclear leukocytes ≥ 1,500/μl or 50% improvement over baseline platelets \> 100,000/μl or 50% improvement over baseline or hemoglobin \> 11.0 gm/dl or 50% improvement over baseline without transfusions

Time frame: At week 9, and post-18 weeks then every 3 months for a year and up every 6 months for up to 2 years

Response rate (complete remission(CR) + partial response(PR)) will be assessed by NCI-WG 1996 criteria with measurements of the lymph nodes and spleen size by CT scans. Best response at any timepoint is captured below. CR= absence of significant lymphadenopathy (e.g. lymph nodes \> 1.5 cm in their greatest transverse diameter) and no hepatomegaly or splenomegaly. PR=reduction in lymphadenopathy as defined by the following: (a) a decrease in lymph node size by 50% or more either in the sum products of up to six lymph nodes, or in the largest diameter of the enlarged lymph node(s) detected prior to therapy; (b) no increase in any lymph node, and no new enlarged lymph node; in small lymph nodes (\< 2cm), an increase of less than 25% was not considered to be significant and a reduction in the noted pretreatment enlargement of the spleen or liver by 50% or more.

Time frame: At week 9, and post-18 weeks then every 3 months for a year and up every 6 months for up to 2 years

Toxicity data will be collected at visits during 18 weeks of treatment and include adverse events considered at least possibly related to either study drugs (Alemtuzumab and Rituximab) and graded 3-5 using CTCAE 3.0. In general grading is as follows: Grade 1=mild Grade 2=moderate Grade 3=severe Grade 4=life threatening Grade 5=death Reported below are the number of patients who experienced each event

Time frame: During treatment, 18 weeks

Patients best response to treatment as defined in general as: Complete Remission=Absence of lymphadenopathy and constitutional symptoms, Normal CBC, peripheral blood lymphocytes ≤ 4,000/μl.The marrow sample must be at least normocellular with \< 30% of nucleated cells being lymphocytes. Partial Remission=absence of constitutional symptoms, ≥50%decrease in peripheral blood lymphocyte count, ≥50%reduction in lymphadenopathy, ≥50%reduction in liver and/or spleen size & 1 of the following: polymorphonuclear leukocytes ≥ 1,500/μl or 50% improvement over baseline, platelets \>100,000/μl or 50%improvement over baseline, hemoglobin \> 11.0 gm/dl or 50% improvement over baseline without transfusions. Stable Disease=Do not meet criteria for complete/partial remission or progressive disease. Progressive Disease= ≥50%increase ≥2 lymph nodes or ≥50% increase in absolute no. of circulating lymphocytes or ≥50% increase in liver and/or spleen size or transformation to a more aggressive histology

Time frame: At week 9, and post 18 weeks of treatment, then every 3 months for a year and up every 6 months for up to 2 years

Best Response to treatment, in general is defined as: Complete Remission= absence of significant lymphadenopathy and no hepatomegaly/splenomegaly. Partial Remission=reduction in lymphadenopathy as defined by the following: (a) 50% decrease in lymph node size by 50% either in the sum products of up to six lymph nodes, or in the largest diameter of the enlarged lymph node(s) detected prior to therapy; (b) no increase in any lymph node, and no new enlarged lymph node; in small lymph nodes (\<2cm),and a reduction in the noted pretreatment enlargement of the spleen or liver by 50% or more. Stable Disease=not meet criteria for complete/partial remission or progressive disease Progressive Disease=appearance of any new lesion, such as enlarged lymph nodes (1.5cm), splenomegaly, hepatomegaly or other organ infiltrates: (a)50%increase + in greatest diameter of any previous site; (b)50% + increase liver or spleen size.

Time frame: At week 9, and post-18 weeks then every 3 months for a year and up every 6 months for up to 2 years