Valproate as First Line Therapy in Combination With Rituximab and CHOP in Diffuse Large B-cell Lymphoma (VALFRID)
Primary Purpose
Diffuse Large B-cell Lymphoma
Status
Completed
Phase
Phase 1
Locations
Sweden
Study Type
Interventional
Intervention
Valproate
Rituximab
Cyclophosphamide
Doxorubicin
Vincristine
Prednisone
Sponsored by
About this trial
This is an interventional treatment trial for Diffuse Large B-cell Lymphoma focused on measuring Lymphoma, Diffuse large B-cell lymphoma, Valproate, R-CHOP, CD 20
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
Sites / Locations
- Skåne University Hospital, Dept. of Oncology
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single, open labeld.
Arm Description
Outcomes
Primary Outcome Measures
Establishment of maximum tolerable dose of valproate.
Secondary Outcome Measures
Full Information
NCT ID
NCT01622439
First Posted
June 12, 2012
Last Updated
March 9, 2018
Sponsor
Lund University Hospital
Collaborators
Valcuria
1. Study Identification
Unique Protocol Identification Number
NCT01622439
Brief Title
Valproate as First Line Therapy in Combination With Rituximab and CHOP in Diffuse Large B-cell Lymphoma
Acronym
VALFRID
Official Title
Valproate as First Line Therapy in Combination With Rituximab and CHOP in Diffuse Large B-cell Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
June 2012 (undefined)
Primary Completion Date
March 2018 (Actual)
Study Completion Date
March 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Lund University Hospital
Collaborators
Valcuria
4. Oversight
Data Monitoring Committee
No
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diffuse Large B-cell Lymphoma
Keywords
Lymphoma, Diffuse large B-cell lymphoma, Valproate, R-CHOP, CD 20
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single, open labeld.
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Valproate
Intervention Description
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
Intervention Name(s)
Rituximab
Intervention Description
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
Intervention Name(s)
Cyclophosphamide
Intervention Description
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
Intervention Name(s)
Doxorubicin
Intervention Description
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
Intervention Name(s)
Vincristine
Intervention Description
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
Intervention Name(s)
Prednisone
Intervention Description
Vill be given orally, 50 mg/m2, day 1-5 every cycle, for a total of 6 cycles.
Primary Outcome Measure Information:
Title
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).
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mats Jerkeman, MD, PhD
Organizational Affiliation
Skåne University Hospital, Dept. of Oncology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Skåne University Hospital, Dept. of Oncology
City
Lund
ZIP/Postal Code
221 85
Country
Sweden
12. IPD Sharing Statement
Citations:
PubMed Identifier
29903707
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.
Results Reference
derived
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Valproate as First Line Therapy in Combination With Rituximab and CHOP in Diffuse Large B-cell Lymphoma
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