A Phase I/II Study of Bortezomib Plus CHOP Every 2 Weeks in Patients With Advanced Stage Diffuse Large B-cell Lymphomas
Intended number of patients: 63 patients in total
- Phase I: 9 patients for 3 levels
- Phase II: 50 patients plus 3 patient from Phase I at MTD level
- Plus 4 patients: considering 5% follow-up loss rate
Study design and methodology:
For phase I, 9 patients; 3 levels of bortezomib (1.0, 1.3 and 1.6 mg/m2), 3 patients at each
If escalation of bortezomib beyond 1.0 mg/m2 is not possible, the trial will be stopped.
For phase II, 53 patients (3 from phase I at MTD level); Reject when complete response rate
equal or less than 12/19 or 37/53 by Simon two-stage optimal phase II design.
For phase I, 3 dose levels (1.0, 1.3 or 1.6 mg/m2), days 1 and 4, every 2 weeks.
For phase II, suggested dose of Bortezomib through phase I, days 1 and 4, every 2 weeks.
- CHOP2: cyclophosphamide 750mg/ m2 day 1, vincristine 1.4 mg/ m2 (max. 2 mg) day 1,
doxorubicin 50 mg/ m2 day 1, prednisolone 100 mg days 1-5, every 2 weeks.
- G-CSF: Lenograstim 5 microgram/kg subcutaneously days 4-13 every 2 weeks.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Patients Who Achieved Complete Response
All patients,9 patients of phase I study and 40 patietns in phase II stuay, were assessed with International Working Group response criteria assessed by CT; Complete Response (CR), Disappearance of all detectable clinical and radiographic evidence of disease and diappearance of all disease-related symptoms.
Cheolwon Suh, M.D.,Ph.D.
Asan Medical Center
Korea: Food and Drug Administration