Valproate as First Line Therapy in Combination With Rituximab and CHOP in Diffuse Large B-cell Lymphoma (VALFRID)
Patients with previously untreated diffuse large B-cell lymphoma will receive standard treatment with R-CHOP (rituximab,cyclosphosphamide, doxorubicin, vincristine, and prednison) for 6 cycles, cycle length is 14 or 21 days. In addition, valproate is given three times daily day 1-3 in escalated doses. The rationale for adding valproate to standard treatment is invitro data indicating a sensitizing effect to chemotherapy, and an increase in CD 20-expression.
Patients are included in 3+3 cohorts with escalation of valproate dose, planned dos levels are 30, 60, 80, 100, 120, 140 mg/kg/day. A total of 20 patients will be treated at the MTD.
|Diffuse Large B-cell Lymphoma||Drug: Valproate Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Valproate as First Line Therapy in Combination With Rituximab and CHOP in Diffuse Large B-cell Lymphoma|
- Establishment of maximum tolerable dose of valproate. [ Time Frame: Participating patients will be followed during study treatment (6 cycles of chemotherapy); 12 weeks or 18 weeks depending on cycle length (14 or 21 days). ]
|Study Start Date:||June 2012|
|Estimated Study Completion Date:||March 2018|
|Estimated Primary Completion Date:||March 2018 (Final data collection date for primary outcome measure)|
|Experimental: Single, open labeld.||
Valproate is given in escalating doses to establish maximum tolerable dose when given together with standard treatment in patients with diffuse large B-cell lymphoma; this is the phase I part of the study. When maximum tolerable dose is established, this dose will be given to remaining patients in the phase II part of the study.Drug: Rituximab
Vill be given intravenously, 375 mg/m2, every second or third week depending on cycle length (14 or 21 days), for a total of 6 cycles.Drug: Cyclophosphamide
Vill be given intravenously, 750 mg/m2, every second or third week depending on cycle length (14 or 21 days) for a total of 6 cycles.Drug: Doxorubicin
Vill be given intravenously, 50 mg/m2, every second or third week depending on cycle length (14 or 21 days), for a total of 6 cycles.Drug: Vincristine
Vill be given intravenously, 1.2 mg/m2, every second or third week depending on cycle length (14 or 21 days), for a total of 6 cycles.Drug: Prednisone
Vill be given orally, 50 mg/m2, day 1-5 every cycle, for a total of 6 cycles.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01622439
|Skåne University Hospital, Dept. of Oncology|
|Lund, Sweden, 221 85|
|Principal Investigator:||Mats Jerkeman, MD, PhD||Skåne University Hospital, Dept. of Oncology|