NCT00829205

Se-Methyl-Seleno-L-Cysteine, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Diffuse Large B-Cell Lymphoma That Has Relapsed or Not Responded to Treatment

A Phase I/II Study of Methylselenocysteine (MSC) in Combination With Immunochemotherapy (R-ICE) in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

• Status: Withdrawn
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Cancer Research UK · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer cell 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 cell-killing substances to them. Drugs used in chemotherapy, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Se-methyl-seleno-l-cysteine may help reduce the side effects of chemotherapy. PURPOSE: This phase I/II trial is studying the side effects and best dose of Se-methyl-seleno-l-cysteine when given together with rituximab, ifosfamide, carboplatin, and etoposide and to see how well it works in treating patients with diffuse large B-cell lymphoma that has relapsed or not responded to treatment.

Detailed description

OBJECTIVES: Primary * To assess dose-limiting toxicity and maximum-tolerated dose (MTD) of Se-methyl-seleno-L-cysteine (MSC) (to achieve a trough serum selenium \[Se\] concentration of \> 20 μmol/L) prior to and in combination with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in patients with relapsed or refractory diffuse large B-cell lymphoma. (Phase I) * To determine the overall response rate to R-ICE given in addition to MSC at the MTD in these patients. (Phase II) Secondary * To determine the toxicity of R-ICE when used in combination with MSC in these patients. * To determine the effect of MSC dosing on serum and intracellular Se and Se species in these patients. * To determine the pharmacokinetics of MSC after single and multiple daily dosing in these patients. * To investigate the effect of MSC dosing on Se-dependent processes (e.g., NFκB activity and AKT). OUTLINE: This is a multicenter, phase I, dose-escalation study of Se-methyl-seleno-L-cysteine (MSC) followed by a phase II study. Patients receive rituximab IV on day 1, carboplatin IV on day 2, ifosfamide IV and etoposide IV on days 2-4 (R-ICE), and filgrastim (G-CSF) subcutaneously on days 6-13. Patients also receive oral MSC twice daily on days -7 to 0 and once daily in courses 1-2. Treatment with R-ICE and G-CSF repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Blood samples are collected periodically and analyzed for pharmacokinetics and protein markers. After completion of study treatment, patients are followed monthly for 3 months. This study is peer reviewed and funded or endorsed by cancer research UK.

Conditions

• Lymphoma

Interventions

Type	Name	Description
BIOLOGICAL	filgrastim
BIOLOGICAL	rituximab
DIETARY_SUPPLEMENT	Se-methyl-seleno-L-cysteine
DRUG	carboplatin
DRUG	etoposide
DRUG	ifosfamide
OTHER	laboratory biomarker analysis
OTHER	pharmacological study

Timeline

• Start date: 2009-01-01
• First posted: 2009-01-26
• Last updated: 2013-08-26

Locations

5 sites across 1 country: United Kingdom