Overview

This trial is active, not recruiting.

Condition diffuse large b-cell lymphoma
Treatments valproate, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone
Phase phase 1/phase 2
Targets CD20, HDAC
Sponsor Lund University Hospital
Collaborator Valcuria
Start date June 2012
End date December 2016
Trial size 50 participants
Trial identifier NCT01622439, Version1.1

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
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.
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.
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.
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.
prednisone
Vill be given orally, 50 mg/m2, day 1-5 every cycle, for a total of 6 cycles.

Primary Outcomes

Measure
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).

Eligibility Criteria

Male or female participants from 18 years up to 80 years old.

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

Additional Information

Official title Valproate as First Line Therapy in Combination With Rituximab and CHOP in Diffuse Large B-cell Lymphoma
Principal investigator Mats Jerkeman, MD, PhD
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Lund University Hospital.