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

Phase 2
Completed
Conditions
Leukemia
Interventions
Biological: Alemtuzumab
Biological: Rituximab
Registration Number
NCT00858117
Lead Sponsor
Northwestern University
Brief Summary

RATIONALE: Monoclonal antibodies, such as alemtuzumab and rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving alemtuzumab together with rituximab may kill more cancer cells.

PURPOSE: This phase II trial is studying the side effects of giving alemtuzumab together with rituximab and to see how well it works in treating patients with previously untreated B-cell chronic lymphocytic leukemia.

Detailed Description

OBJECTIVES:

* To determine the response rate in patients with previously untreated B-cell chronic lymphocytic leukemia treated with alemtuzumab and rituximab.

* To evaluate the toxicity of alemtuzumab and rituximab in these patients.

OUTLINE: Patients receive alemtuzumab subcutaneously on days 1, 3, and 5 in weeks 1-18 and rituximab IV on day 1 in weeks 3, 5, 7, 9, 11, 13, 15, and 17 in the absence of disease progression or unacceptable toxicity.

Peripheral blood and bone marrow samples are collected periodically for laboratory biomarker studies. Samples are analyzed for surface markers (e.g., CD3, CD4, CD8, CD10, CD19, CD20, CD25, CD38, CD52, Zap-70) and IgVH by PCR, flow cytometry, and FISH. Samples are also analyzed for alemtuzumab and anti-alemtuzumab antibody levels by flow cytometry.

After completion of study treatment, patients are followed periodically for 5 years.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Alemtuzumab and RituximabAlemtuzumabAdministration of Alemtuzumab combined with Rituximab to test the feasibility of combining these two monoclonal antibodies as a first line therapy in patients with B-cell chronic lymphocytic leukemia.
Alemtuzumab and RituximabRituximabAdministration of Alemtuzumab combined with Rituximab to test the feasibility of combining these two monoclonal antibodies as a first line therapy in patients with B-cell chronic lymphocytic leukemia.
Primary Outcome Measures
NameTimeMethod
Number of Patients Treated With Alemtuzumab and Rituximab Combination With Response (CR or PR) Assessed by NCI-WG 1996 Criteria With Measurements of the Lymph Nodes and Spleen Size by CT ScansAt 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.

Number of Patients Treated With Alemtuzumab and Rituximab Combination With a Response (CR or PR) Assessed by NCI-WG 1996 Criteria With Lymph-adenopathy and Organomegaly Measured During Physical ExaminationAt 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 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

Secondary Outcome Measures
NameTimeMethod
Toxicity of the Study Medications, Alemtuzumab and RituximabDuring treatment, 18 weeks

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

Trial Locations

Locations (1)

Northwestern University, Northwestern Medical Faculty Foundation

🇺🇸

Chicago, Illinois, United States

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