Clofarabine and Rituximab in Treating Patients With Relapsed Non-Hodgkin Lymphoma

Lymphoma Clinical Trial

Official title: Phase I/II Study of Oral Clofarabine + Rituximab in Relapsed B Cell NHL

Status Terminated

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as clofarabine, 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 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 clofarabine together with rituximab may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine when given together with rituximab and to see how well they work in treating patients with relapsed B-cell non-Hodgkin lymphoma.

Clinical Trial Description

OBJECTIVES:

Primary

• To determine the maximum tolerated dose of clofarabine in adult patients with relapsed CD20-positive B-cell non-Hodgkin lymphoma (NHL).

• To estimate objective response rates of clofarabine in combination with rituximab in these patients.

Secondary

• To determine the 1-year progression-free survival of this regimen using the mean tolerated dose in these patients.

• To determine the safety and efficacy of this regimen in these patients.

• To determine if clofarabine acts as an inhibitor of DNA methylation similar to cladribine by performing scientific correlates.

• To determine whether response to clofarabine alone or in combination with rituximab correlates with changes in global serum DNA methylation index.

• To identify the gene activated by clofarabine therapy by using genomic DNA and RNA array technology.

OUTLINE: This is a phase I, dose-escalation study of clofarabine followed by a phase II study.

Patients receive oral clofarabine once daily on days 1-14 of all courses and rituximab IV on days 1, 8, 15, and 22 of course one and then on day 1 of courses 2-8. Courses repeat every 4 weeks. After 2 courses of therapy, patients who are eligible for stem cell transplantation may either undergo transplantation or continue receiving study drugs until disease progression or unacceptable toxicity for up to a total of 8 courses of treatment.

Patients undergo blood sample collection periodically for correlative studies. Samples are analyzed to identify global DNA methylation differences and correlate changes in methylation index (MI) with patient outcome after treatment with clofarabine with or without rituximab via high performance liquid chromatography (HPLC); to determine differences in gene expression via microarray analysis and micro-RNA (miRNA) expression via quantitative polymerase chain reaction (PCR) in patients with high compared to low global DNA methylation index and miRNA expression for CD5+ B-lymphocytes obtained from pediatric tonsils and from B-lymphocytes of 5 healthy controls; and to determine gene expression and miRNA profiles in patients before and after treatment with clofarabine with or without rituximab via genomic DNA arrays.

After completion of study treatment, patients are followed once a year for 2 years. ;

Related Conditions & MeSH terms

• Lymphoma

• NCT number: NCT00691652
• Study type: Interventional
• Source: OHSU Knight Cancer Institute
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: May 2008
• Completion date: April 2009