Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) With Pentostatin, Alemtuzumab, and Low Dose Rituximab: A Phase II Clinical Trial
- To assess the rate of complete and overall response in patients with relapsed or
refractory chronic lymphocytic leukemia or small lymphocytic lymphoma treated with
pentostatin, alemtuzumab, and low-dose rituximab.
- To assess response to this treatment regimen using an expanded definition of response,
including CT scans of chest-abdomen-pelvis, immunohistochemical analysis for residual
disease in the bone marrow, and sensitive flow cytometry for minimal residual disease
in patients who achieve a complete clinical remission.
- To monitor and assess toxicity of this treatment regimen.
- To determine the overall and progression-free survival, duration of response, and time
to next treatment.
- To assess the correlation between individual prognostic markers (17p-, 11q-, unmutated
VH gene, VH3-21, ZAP-70+, CD38+, CD49d, and β2 microglobulin, miRNA profiles,
angiogenesis status, and karyotypes of CpG stimulated cells) and clinical outcome.
- Measure the effect of monoclonal antibody concentration on the complement
fixation-antibody dependent cellular cytotoxicity interaction.
- Assess minimal residual disease status in responding patients using sensitive flow
cytometry and correlate with overall and progression-free survival, duration of
response, and time to next treatment.
- Detail the in vivo effect of this treatment regimen on critical aspects of the immune
system in these patients.
OUTLINE: This is a multicenter study.
- Course 1: Patients receive pentostatin IV on days 8 and 22; alemtuzumab subcutaneously
(SC) on days 3-5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; rituximab IV on
days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33; and sargramostim
(GM-CSF) SC on days 10-14 and 24-28. Patients then proceed to course 2.
- Courses 2 and 3: Patients receive pentostatin IV on days 1 and 15; alemtuzumab SC and
rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26; and GM-CSF SC on
days 3-7 and 17-21. After completion of course 2, patients with a complete response
proceed to observation. Patients with a partial response or stable disease receive
another course of therapy (course 3).
Treatment continues in the absence of disease progression or unacceptable toxicity.
Blood is collected on days 1, 3, 8, and 10 of course 1 for monoclonal antibody studies.
Samples are analyzed for serum concentration of alemtuzumab and rituximab by ELISA and PCR;
CH50 assay; complement activation and cytokine levels by ELISA; NK cell activation; and NK
cell phenotype by immunofluorescent staining and flow cytometry.
After completion of study treatment, patients are followed up monthly for 6 months, every 3
months for 6 months, and then every 6-12 months for up to 5 years.
Masking: Open Label, Primary Purpose: Treatment
Proportion of complete responses
Clive S. Zent, MD
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|
|Holden Comprehensive Cancer Center at University of Iowa||Iowa City, Iowa 52242-1002|
|University of Virginia Cancer Center||Charlottesville, Virginia 22908|