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

NCT ID: NCT01622439

Last Updated: 2018-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-06-30
• Study Completion Date: 2018-03-31

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.

Conditions

Diffuse Large B-cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single, open labeld.

Group Type: EXPERIMENTAL

Valproate

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Vill be given orally, 50 mg/m2, day 1-5 every cycle, for a total of 6 cycles.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Prednisone

Vill be given orally, 50 mg/m2, day 1-5 every cycle, for a total of 6 cycles.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Valcuria

UNKNOWN

Sponsor Role: collaborator

Lund University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mats Jerkeman, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Skåne University Hospital, Dept. of Oncology

Locations

Skåne University Hospital, Dept. of Oncology

Lund, , Sweden

Countries

Sweden

References

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.

Reference Type: DERIVED

PMID: 29903707 (View on PubMed)

Other Identifiers

Version1.1

Identifier Type: -

Identifier Source: org_study_id