Alemtuzumab and Rituximab in Treating Patients With High-Risk, Early-Stage Chronic Lymphocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00436904
Recruitment Status : Completed
First Posted : February 19, 2007
Results First Posted : October 26, 2011
Last Update Posted : December 1, 2011
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Mayo Clinic

February 15, 2007
February 19, 2007
September 16, 2011
October 26, 2011
December 1, 2011
December 2004
July 2008   (Final data collection date for primary outcome measure)
  • Confirmed Response, Defined as Objective Complete Remission or Partial Remission for a Duration of at Least 2 Months [ Time Frame: Up to 6 months ]
    Confirmed response is defined as a > 50% decrease in clinical symptoms from baseline and recovery from blood counts.
  • Number of Participants With Treatment Related Adverse Events [ Time Frame: Weekly for first 6 weeks, then monthly for 6 months, then at 9 and 12 months post registration ]

    Adverse events (AE) that are classified as either possibly, probably, or definitely related to study treatment according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE version 3.0). The maximum grade for each type of AE will be recorded for each patient. Grade refers to the severity of the AE.


    > Grade 1: Mild AE, Grade 2: Moderate AE, Grade 3: Severe AE, Grade 4: Life-threatening or disabling AE, Grade 5: Death related AE

  • Confirmed response, defined as objective status of complete remission or partial remission for a duration of at least 2 months
  • Toxicity
Complete list of historical versions of study NCT00436904 on Archive Site
  • Time to Response [ Time Frame: Registration to first response (up to 5 years) ]
    Calculated from the date of registration until the first date at which the patient's objective status was classified as a response. In patients who do not achieve a response, time to response will be censored at the patient's last evaluation date. Response is defined the same way as in the response primary outcome measure.
  • Duration of Response [ Time Frame: Up to 5 years ]
    Duration of response is calculated from the date of documented response until the date of progression in the subset of patients who respond to treatment. In patients who have not yet progressed, duration of response will be censored at the patient's last evaluation date.
  • Survival [ Time Frame: Death or last follow-up (up to 5 years) ]
    Survival is calculated from the date of registration to the date of death due to any cause. In patients who are still alive, survival will be censored at the last date when the patient was known to be alive.
  • Time to Disease Progression [ Time Frame: Time from registration to progression (up to 5 years) ]
    Calculated from date of registration to date of disease progression. In patients that have not progressed, time to disease progression will be censored at the patient's last evaluation date.
  • Time to Response
  • Duration of Response
  • Survival
  • Time to Disease Progression
Not Provided
Not Provided
Alemtuzumab and Rituximab in Treating Patients With High-Risk, Early-Stage Chronic Lymphocytic Leukemia
Antibody Therapy With Alemtuzumab and Rituximab for Initial Treatment of High Risk Chronic Lymphocytic Leukemia

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 and how well giving alemtuzumab together with rituximab works in treating patients with high-risk, early-stage chronic lymphocytic leukemia.



  • Determine the rate of complete and overall response to alemtuzumab and rituximab in patients with high-risk, early-stage chronic lymphocytic leukemia.
  • Determine the toxicity of this regimen in these patients. Secondary
  • Determine the overall survival and time to progression of patients treated with this regimen.
  • Determine time to response and duration of response in patients treated with this regimen.
  • Correlate prognostic markers 11q-, 17p-, unmutated VH gene, and CD38+ with clinical outcome.
  • Determine response to this regimen using an expanded definition of response that includes minimal residual disease detected by sensitive flow cytometry in patients in complete clinical remission and single rearranged IgVH gene detected by polymerase chain reaction in patients with no monoclonal population on flow cytometry.
  • Correlate in vitro response with clinical outcome in patients treated with this regimen.
  • Determine if alemtuzumab and rituximab are synergistic in vitro.
  • Determine the mechanism of action of this regimen in vitro.
  • Determine the effect of this regimen on immune function.
  • Monitor T-lymphocyte, natural killer cell, and monocyte number during and after treatment in these patients.
  • Serially evaluate T-lymphocyte immunophenotype and function in patients treated with this regimen.
  • Monitor recovery of humoral immunity by serial serum protein electrophoresis, immunofixation electrophoresis, and immunoglobulin quantification.


  • Dose-escalation (week 1): Patients receive rituximab IV on day 1 and escalating doses of alemtuzumab subcutaneously (SC) on days 3-5 in week 1.
  • Treatment (weeks 2-5): Patients receive alemtuzumab SC on days 1-3 (at the highest dose administered during week 1) and rituximab IV on day 3 in weeks 2-5 in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection at baseline and periodically during study treatment for pharmacokinetic and prognostic biomarker (11q-, 17p-, unmutated IgVH, and CD38 expression by flow cytometry and fluorescent in-situ hybridization) studies. Immune function (CDR3 T-cell receptor by reverse transcriptase-polymerase chain reaction) and in vitro and in vivo response are also examined.

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

PROJECTED ACCRUAL: A total of 33 patients will be accrued for this study.

Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Drug: Alemtuzumab
    30 mg Monday, Wednesday, and Friday x 5 weeks
  • Drug: Rituximab
    375mg/m2 IV weekly (Wednesday) x 4 weeks (weeks 2-5)
Experimental: Alemtuzumab + Rituximab
Alemtuzumab 30mg Monday, Wednesday, and Friday x 5 weeks, Rituximab 375/mg/m2 IV weekly (Wednesday) x 4 weeks (weeks 2-5)
  • Drug: Alemtuzumab
  • Drug: Rituximab

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
November 2011
July 2008   (Final data collection date for primary outcome measure)


* Diagnosis of B-cell chronic lymphocytic leukemia (CLL)

- Early-stage, biologically high-risk disease defined by the following criteria:

  • Rai stage 0-II (does not meet standard NCI-sponsored Working Group criteria for treatment)
  • Clinical and phenotypic features manifested in the peripheral blood, including the following:

    • Minimum threshold peripheral blood lymphocyte count of > 5,000/mm³
    • Small-to-moderate peripheral blood lymphocytes with ≤ 55% prolymphocytes
    • Monoclonality of B lymphocytes by immunophenotypic evaluation, demonstrating co-expression of CD19, CD5, and CD23 antigens, surface expression of CD20 and CD52, and B-cell monoclonal population defined by light-chain exclusions
  • Poor prognosis demonstrated by ≥ 1 of the following high-risk parameters:

    • Unmutated human immunoglobulin variable region heavy chain (IgVH) gene and CD38 expression (≥ 30% cells positive on flow cytometry) OR unmutated IgVH ZAP-70 expression (≥ 20% cells positive on flow cytometry) = 11q- = 17p-


  • ECOG performance status 0-2
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Total bilirubin ≤ 3.0 times ULN OR direct bilirubin ≤ 1.5 times ULN
  • AST ≤ 3.0 times ULN (unless due to hemolysis or CLL)
  • Hemoglobin ≥ 9.0 g/dL
  • No New York Heart Association class III-IV heart disease
  • No myocardial infarction within the past month
  • No uncontrolled infection
  • No active HIV infection
  • No evidence of autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
  • No other active primary malignancy requiring treatment or limiting survival to less than 2 years


  • No prior treatment for CLL
  • Prior corticosteroids allowed
  • No prior radiotherapy
  • More than 4 weeks since prior major surgery
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
P30CA015083 ( U.S. NIH Grant/Contract )
MC038G ( Other Identifier: Mayo Clinic Cancer Center )
801-04 ( Other Identifier: Mayo Clinic IRB )
106.G0309 ( Other Identifier: Bayer and Berlex protocol )
U3023s ( Other Identifier: Genentech Protocol )
Not Provided
Not Provided
Mayo Clinic
Mayo Clinic
National Cancer Institute (NCI)
Study Chair: Clive S. Zent, MD Mayo Clinic
Mayo Clinic
November 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP