NCT01622439

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
50

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jun 2012

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2012

Completed
11 days until next milestone

First Submitted

Initial submission to the registry

June 12, 2012

Completed
7 days until next milestone

First Posted

Study publicly available on registry

June 19, 2012

Completed
5.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2018

Completed
Last Updated

March 12, 2018

Status Verified

September 1, 2016

Enrollment Period

5.8 years

First QC Date

June 12, 2012

Last Update Submit

March 9, 2018

Conditions

Keywords

LymphomaDiffuse large B-cell lymphomaValproateR-CHOPCD 20

Outcome Measures

Primary Outcomes (1)

  • 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).

Study Arms (1)

Single, open labeld.

EXPERIMENTAL
Drug: ValproateDrug: RituximabDrug: CyclophosphamideDrug: DoxorubicinDrug: VincristineDrug: Prednisone

Interventions

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.

Single, open labeld.

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.

Single, open labeld.

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.

Single, open labeld.

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.

Single, open labeld.

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.

Single, open labeld.

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

Single, open labeld.

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Skåne University Hospital, Dept. of Oncology

Lund, 221 85, Sweden

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Lymphoma, Large B-Cell, DiffuseLymphoma

Interventions

Valproic AcidRituximabCyclophosphamideDoxorubicinVincristinePrednisone

Condition Hierarchy (Ancestors)

Lymphoma, B-CellLymphoma, Non-HodgkinNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Pentanoic AcidsValeratesAcids, AcyclicCarboxylic AcidsOrganic ChemicalsFatty Acids, VolatileFatty AcidsLipidsAntibodies, Monoclonal, Murine-DerivedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsPhosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsPhosphoramidesOrganophosphorus CompoundsDaunorubicinAnthracyclinesNaphthacenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicPolycyclic CompoundsAminoglycosidesGlycosidesCarbohydratesVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizinesPregnadienediolsPregnadienesPregnanesSteroidsFused-Ring Compounds

Study Officials

  • Mats Jerkeman, MD, PhD

    Skåne University Hospital, Dept. of Oncology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 12, 2012

First Posted

June 19, 2012

Study Start

June 1, 2012

Primary Completion

March 1, 2018

Study Completion

March 1, 2018

Last Updated

March 12, 2018

Record last verified: 2016-09

Locations