Trial Information

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)

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.