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)
- 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)
- 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
- To determine the pharmacokinetics of MSC after single and multiple daily dosing in
- To investigate the effect of MSC dosing on Se-dependent processes (e.g., NFκB activity
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
Blood samples are collected periodically and analyzed for pharmacokinetics and protein
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.
Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity and maximum tolerated dose of Se-methyl-seleno-L-cysteine (MSC) (Phase I)
Silvia Montoto, MD
Barts and the London NHS Trust