Clinical trial NCT00669318
Conditions: Leukemia Lymphoma
Keywords: refractory chronic lymphocytic leukemia recurrent small lymphocytic lymphoma B-cell chronic lymphocytic leukemia
Sponsor: Mayo Clinic
Start date: 2008-07-01; Completion date: 2014-05-01
Enrollment: 41 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
OBJECTIVES:

Primary

* 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 monitor and assess toxicity of this treatment regimen.

Secondary

* 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.

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.

Arms: arm 1: Course 1: Patients receive:

* 2 mg/m\^2 pentostatin IV on days 8 and 22;
* 3 mg alemtuzumab subcutaneously (SC) on day 3;
* 10 mg alemtuzumab SC on day 4;
* 30 mg alemtuzumab SC on days 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33;
* 20 mg/m\^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33;
* 6 mg Sargramostim (GM-CSF) SC on days 10-14. Patients then proceed to course 2.

Courses 2 and 3: Patients receive:

* 2 mg/m\^2 pentostatin IV on days 1 and 15;
* 30 mg alemtuzumab SC on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26;
* 20 mg/m\^2 rituximab IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, and 26;
* 6 mg GM-CSF SC on days 3-7. 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).
Interventions: intervention 1: alemtuzumab intervention 2: rituximab intervention 3: pentostatin intervention 4: sargramostim
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol documents: