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

Study Overview
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Brief Summary
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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.

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

Conditions
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Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Drug: Valproate
* Drug: Rituximab
* Drug: Cyclophosphamide
* Drug: Doxorubicin
* Drug: Vincristine
* Drug: Prednisone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single, open labeld.<br> | Drug: Valproate<br>* 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.<br>Drug: Rituximab<br>* 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.<br>Drug: Cyclophosphamide<br>* 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.<br>Drug: Doxorubicin<br>* 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.<br>Drug: Vincristine<br>* 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.<br>Drug: Prednisone<br>* Vill be given orally, 50 mg/m2, day 1-5 every cycle, for a total of 6 cycles.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Establishment of maximum tolerable dose of valproate. |  | 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). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Diffuse large B-cell lymphoma, Valproate, R-CHOP, CD 20