Rituximab, Cladribine, and Temsirolimus in Treating Patients With Newly Diagnosed Mantle Cell Lymphoma
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Trial of Rituximab, Cladribine, and Temsirolimus (RCT) Therapy in Newly Diagnosed Mantle Cell Lymphoma (MCL)|
- Number of dose limiting toxicity incidents as per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 3.0 (Phase I) [ Time Frame: 28 days ]
- Proportion of complete tumor responses defined as complete remission (CR) as the objective status (Phase II) [ Time Frame: Up to 5 years ]
- Overall survival [ Time Frame: up to 5 years ]
- Progression-free survival (PFS) [ Time Frame: up to 5 years ]
- Time to disease progression [ Time Frame: up to 5 years ]
- Duration of response, defined as date at which the patient's objective status is first noted to be either a CR or partial remission to the date progression is documented [ Time Frame: Up to 5 years ]
- Survival time [ Time Frame: Up to 5 years ]
- Frequency and severity of adverse events assessed by CTCAE v3.0 [ Time Frame: Up to 5 years ]
|Study Start Date:||April 2009|
|Primary Completion Date:||April 2012 (Final data collection date for primary outcome measure)|
Experimental: Treatment (rituximab, cladribine, temsirolimus)
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 days 1, 8, 15, and 22. Patients also receive filgrastim 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.
Give IVDrug: cladribine
Give IVDrug: temsirolimus
Give IVBiological: Filgrastim
Give SCBiological: Pegfilgrastim
I. To assess the efficacy and safety of the combination of rituximab, cladribine, and temsirolimus for newly diagnosed mantle cell lymphoma.
II. To determine the maximum tolerated dose (MTD) of temsirolimus combined with a fixed dose and schedule of rituximab and cladribine. (Phase I) III. To assess the efficacy of the combination of rituximab, cladribine, and temsirolimus for newly diagnosed mantle cell lymphoma with the proportion of complete responses as the primary endpoint. (Phase II)
I. To assess other measures of efficacy of the regimen including progression free survival, duration of response, and overall survival.
II. To assess the toxicity profile of the combination of rituximab, cladribine, and temsirolimus.
III. To assess efficacy using traditional lymphoma parameters and absolute lymphocyte count.
IV. To assess metabolic markers (hyperglycemia, hyperlipidemia) as markers of mammalian target of rapamycin (mTOR) inhibition using the glucose and lipid measurements being performed in the clinical laboratory as part of routine care.
V. To correlate response with serum free light chains, single nucleotide polymorphisms (SNPs) in host immune genes, vitamin D metabolites, and phosphatidylinositide 3-kinase (PI3K) pathway member expression.
VI. As part of ongoing research for North Central Cancer Treatment Group (NCCTG) lymphoma studies, paraffin-embedded tissue blocks/slides and blood products will be banked for future studies.
OUTLINE: This is a phase I, dose-escalation study of temsirolimus followed by a phase II study.
Patients receive rituximab intravenously (IV) on day 1 and cladribine IV over 2 hours on days 1-5. Patients then receive temsirolimus IV over 30 minutes on days 1, 8, 15, and 22. Patients also receive filgrastim 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.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 4 months for 3 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00787969
Show 144 Study Locations
|Study Chair:||David J. Inwards, MD||Mayo Clinic|