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

Sponsor

Lund University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01622439

Collaborator

Valcuria (Other)

Enrollment

Location

Arm

Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diffuse Large B-cell Lymphoma	Drug: Valproate Drug: Rituximab Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Mar 1, 2018

Actual Study Completion Date :

Mar 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Single, open labeld.	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.

Arm

Intervention/Treatment

Experimental: Single, open labeld.

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.

Outcome Measures

Primary Outcome Measures

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).]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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