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
- 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.
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Confirmed Response, Defined as Objective Complete Remission or Partial Remission for a Duration of at Least 2 Months
Confirmed response is defined as a > 50% decrease in clinical symptoms from baseline and recovery from blood counts.
Up to 6 months
Clive S. Zent, MD
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|