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Antibody Therapy With Alemtuzumab and Rituximab for Initial Treatment of High Risk Chronic Lymphocytic Leukemia

Phase 2
18 Years
Not Enrolling

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Trial Information

Antibody Therapy With Alemtuzumab and Rituximab for Initial Treatment of High Risk 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

- Determine time to response and duration of response in patients treated with this

- Correlate prognostic markers 11q-, 17p-, unmutated VH gene, and CD38+ with clinical

- 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

- 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.

Inclusion Criteria


* 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

- Clinical and phenotypic features manifested in the peripheral blood, including the

- 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

Type of Study:


Study Design:

Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Confirmed Response, Defined as Objective Complete Remission or Partial Remission for a Duration of at Least 2 Months

Outcome Description:

Confirmed response is defined as a > 50% decrease in clinical symptoms from baseline and recovery from blood counts.

Outcome Time Frame:

Up to 6 months

Safety Issue:


Principal Investigator

Clive S. Zent, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Mayo Clinic


United States: Food and Drug Administration

Study ID:




Start Date:

December 2004

Completion Date:

November 2011

Related Keywords:

  • Leukemia
  • stage 0 chronic lymphocytic leukemia
  • stage I chronic lymphocytic leukemia
  • stage II chronic lymphocytic leukemia
  • B-cell chronic lymphocytic leukemia
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid



Mayo Clinic Rochester, Minnesota  55905