Valproate as First Line Therapy in Combination With Rituximab and CHOP in Diffuse Large B-cell Lymphoma | RxWiki

Valproate as First Line Therapy in Combination With Rituximab and CHOP in Diffuse Large B-cell Lymphoma

Overview[ - collapse ][ - ]

Purpose	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.
Condition	Diffuse Large B-cell Lymphoma
Intervention	Drug: Valproate Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone
Phase	Phase 1/Phase 2
Sponsor	Lund University Hospital
Responsible Party	Lund University Hospital
ClinicalTrials.gov Identifier	NCT01622439
First Received	June 12, 2012
Last Updated	April 25, 2014
Last verified	April 2014

Tracking Information[ + expand ][ + ]

First Received Date	June 12, 2012
Last Updated Date	April 25, 2014
Start Date	June 2012
Estimated Primary Completion Date	December 2014
Current Primary Outcome Measures	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).] [Designated as safety issue: Yes]
Current Secondary Outcome Measures	Not Provided

Descriptive Information[ + expand ][ + ]

Brief Title	Valproate as First Line Therapy in Combination With Rituximab and CHOP in Diffuse Large B-cell Lymphoma
Official Title	Valproate as First Line Therapy in Combination With Rituximab and CHOP in Diffuse Large B-cell Lymphoma
Brief Summary	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.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 1/Phase 2
Study Design	Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Diffuse Large B-cell Lymphoma
Intervention	Drug: Valproate 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.
Study Arm (s)	Not Provided

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	50
Estimated Completion Date	December 2014
Estimated Primary Completion Date	December 2014
Eligibility Criteria	Inclusion Criteria: - Age 18-80 years - Histologically confirmed (according to the WHO classification) diffuse large B-cell lymphoma stage II-IV - No previous treatment for lymphoma. Corticosteroids for alleviation of lymphoma associated symptoms are allowed - WHO performance status 0-2 - HIV negativity - Seronegativity for HCV, HBsAg, anti-HBc, or other active infection uncontrolled by treatment - Absence of psychiatric illness or condition which could interfere with the subjects ability understand the requirements of the study - Absence of neurological or neuropsychiatric disorder, interfering with the requirements of the study - Absence of hearing impairment > grade 2 - Absence of porphyria - In females: absence of pregnancy and lactation - All subjects must agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy - All subjects must agree not to share study medication with another person, and to return all unused study drug to investigators - Written informed concent according to ICH/GCP and Swedish regulations
Gender	Both
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Mats Jerkeman, MD, PhD +46 46 17 75 20 mats.jerkeman@med.lu.se
Location Countries	Sweden

Administrative Information[ + expand ][ + ]

NCT Number	NCT01622439
Other Study ID Numbers	Version1.1
Has Data Monitoring Committee	No
Information Provided By	Lund University Hospital
Study Sponsor	Lund University Hospital
Collaborators	Valcuria
Investigators	Principal Investigator: Mats Jerkeman, MD, PhD Skåne University Hospital, Dept. of Oncology
Verification Date	April 2014

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