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

Diffuse Large B-cell Lymphoma Clinical Trial

— VALFRID  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01622439
• Other study ID #: Version1.1
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 12, 2012
• Last updated: March 9, 2018
• Start date: June 2012
• Est. completion date: March 2018

Study information

• Verified date: September 2016
• Source: Lund University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: March 2018
• Est. primary completion date: March 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

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.
• 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.

Locations

Country	Name	City	State
Sweden	Skåne University Hospital, Dept. of Oncology	Lund

Sponsors (2)

Lead Sponsor	Collaborator
Lund University Hospital	Valcuria

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).