Clinical trial NCT01622439: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Diffuse Large B-cell Lymphoma
Keywords: Lymphoma
Diffuse large B-cell lymphoma
Valproate
R-CHOP
CD 20
Lead sponsor: Lund University Hospital
Sponsor class: OTHER
Collaborators: name: Valcuria
First posted: 2012-06-19
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Establishment of maximum tolerable dose of valproate.
timeFrame: 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).
Secondary outcomes:
Other outcomes:
Locations:
city: Lund
country: Sweden
facility: Skåne University Hospital, Dept. of Oncology
Study officials:
affiliation: Skåne University Hospital, Dept. of Oncology
name: Mats Jerkeman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Drott K, Hagberg H, Papworth K, Relander T, Jerkeman M. Valproate in combination with rituximab and CHOP as first-line therapy in diffuse large B-cell lymphoma (VALFRID). Blood Adv. 2018 Jun 26;2(12):1386-1392. doi: 10.1182/bloodadvances.2018019240.