Pentostatin, Alemtuzumab, and Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
RATIONALE: Drugs used in chemotherapy, such as pentostatin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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 pentostatin together with alemtuzumab and rituximab may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving pentostatin together with alemtuzumab and rituximab works in treating patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.
Genetic: polymerase chain reaction
Other: flow cytometry
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
|Study Design:||Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Treatment of Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL) With Pentostatin, Alemtuzumab, and Low Dose Rituximab: A Phase II Clinical Trial|
- Proportion of complete responses [ Designated as safety issue: No ]
- Overall response rate (complete and partial response) [ Designated as safety issue: No ]
- Overall survival [ Designated as safety issue: No ]
- Progression-free survival [ Designated as safety issue: No ]
- Duration of response [ Designated as safety issue: No ]
- Time to subsequent therapy [ Designated as safety issue: No ]
- IgVh gene mutation, CD38, ZAP-70, CD49d, and FISH status of chronic lymphocytic leukemia clones [ Designated as safety issue: No ]
|Study Start Date:||July 2008|
|Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
- 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.
|United States, Iowa|
|Holden Comprehensive Cancer Center at University of Iowa|
|Iowa City, Iowa, United States, 52242-1002|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, Virginia|
|University of Virginia Cancer Center|
|Charlottesville, Virginia, United States, 22908|
|Study Chair:||Clive S. Zent, MD||Mayo Clinic|