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

Lund University Hospital

Status and phase: Completed; Phase 2; Phase 1

Conditions: Diffuse Large B-cell Lymphoma

Treatments: Drug: Prednisone; Drug: Vincristine; Drug: Valproate; Drug: Cyclophosphamide; Drug: Rituximab; Drug: Doxorubicin

Study type: Interventional

Funder types: Other

Identifiers

NCT01622439

Version1.1

Details and patient eligibility

About

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.

Enrollment: 50 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

Single, open labeld.

Experimental group

Treatment:

Drug: Prednisone

Drug: Cyclophosphamide

Drug: Rituximab

Drug: Valproate

Drug: Vincristine

Drug: Doxorubicin