Rituximab, Cladribine, and Temsirolimus in Treating Patients With Newly Diagnosed Mantle Cell Lymphoma
Recruitment status was Active, not recruiting
RATIONALE: 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. Drugs used in chemotherapy, such as cladribine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Temsirolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving temsirolimus together with cladribine and rituximab may kill more cancer cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of temsirolimus when given together with cladribine and rituximab and to see how well it works in treating patients with newly diagnosed mantle cell lymphoma.
Genetic: cytogenetic analysis
Genetic: gene expression analysis
Genetic: protein expression analysis
Other: laboratory biomarker analysis
Other: liquid chromatography
Other: mass spectrometry
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Phase I/II Trial of Rituximab, Cladribine, and Temsirolimus (RCT) Therapy in Newly Diagnosed Mantle Cell Lymphoma (MCL)|
- Maximum tolerated dose of temsirolimus (Phase I) [ Designated as safety issue: Yes ]
- Number of dose limiting toxicity incidents as assessed by NCI CTCAE v3.0 (Phase I) [ Designated as safety issue: Yes ]
- Proportion of complete tumor responses [ Designated as safety issue: No ]
- Toxicity profile as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
- Overall survival [ Designated as safety issue: No ]
- Progression-free survival [ Designated as safety issue: No ]
- Time to disease progression [ Designated as safety issue: No ]
- Duration of response [ Designated as safety issue: No ]
- Correlation of traditional lymphoma parameters as well as absolute lymphocyte count, serum free light chains, and PI3K pathway member expression with response [ Designated as safety issue: No ]
|Study Start Date:||April 2009|
|Estimated Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
- To assess the efficacy and safety of the combination of rituximab, cladribine, and temsirolimus in patients with newly diagnosed mantle cell lymphoma.
- To determine the maximum tolerated dose of temsirolimus combined with a fixed dose and schedule of rituximab and cladribine in these patients. (Phase I)
- To assess the efficacy of this regimen, in terms of proportion of complete responses in these patients. (Phase II)
- To assess other measures of efficacy of this regimen, including progression-free survival, duration of response, and overall survival of these patients.
- To assess the toxicity profile of this regimen in these patients.
- To assess efficacy using traditional lymphoma parameters and absolute lymphocyte count.
- To assess metabolic markers (i.e., hyperglycemia and hyperlipidemia) as markers of mTOR inhibition using the glucose and lipid measurements being performed in the clinical laboratory as part of routine care for these patients.
- To correlate response in these patients with serum free light chains, single nucleotide polymorphisms in host immune genes, vitamin D metabolites, and PI3K pathway member expression.
OUTLINE: This is a phase I, dose-escalation study of temsirolimus followed by a phase II study.
Patients receive rituximab IV on day 1 and cladribine IV over 2 hours on days 1-5. Patients then receive temsirolimus IV over 30 minutes on day 1; on days 1 and 15; on days 1, 8, and 15; or on days 1, 8, 15, and 22*. Patients also receive filgrastim (G-CSF) subcutaneously (SC) on days 6-15 or pegfilgrastim SC on day 6. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
NOTE: *Patients enrolled in phase II receive temsirolimus at the maximum tolerated dose determined in phase I following a fixed schedule in a 28-day course.
Blood and tissue samples are collected at baseline and after course 2 for laboratory correlative studies. Samples are analyzed for serum free light chains, single nucleotide polymorphisms in host immune genes, vitamin D metabolites by liquid chromatography/tandem mass spectrometry, clinical metabolic markers (i.e., hyperglycemia or hyperlipidemia) as markers of mTOR inhibition, and PI3K pathway member expression.
After completion of study treatment, patients are followed periodically for up to 5 years.