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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by Lund University Hospital
Sponsor:
Collaborator:
Valcuria
Information provided by (Responsible Party):
Lund University Hospital
ClinicalTrials.gov Identifier:
NCT01622439
First received: June 12, 2012
Last updated: February 16, 2016
Last verified: February 2016
  Purpose

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 Intervention Phase
Diffuse Large B-cell Lymphoma
Drug: Valproate
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Vincristine
Drug: Prednisone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Valproate as First Line Therapy in Combination With Rituximab and CHOP in Diffuse Large B-cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Lund University Hospital:

Primary Outcome Measures:
  • 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). ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: June 2012
Estimated Study Completion Date: June 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01622439

Contacts
Contact: Mats Jerkeman, MD, PhD +46 46 17 75 20 mats.jerkeman@med.lu.se

Locations
Sweden
Skåne University Hospital, Dept. of Oncology Recruiting
Lund, Sweden, 221 85
Contact: Mats Jerkeman, MD, PhD         
Sponsors and Collaborators
Lund University Hospital
Valcuria
Investigators
Principal Investigator: Mats Jerkeman, MD, PhD Skåne University Hospital, Dept. of Oncology
  More Information

Responsible Party: Lund University Hospital
ClinicalTrials.gov Identifier: NCT01622439     History of Changes
Other Study ID Numbers: Version1.1 
Study First Received: June 12, 2012
Last Updated: February 16, 2016
Health Authority: Sweden: Medical Products Agency

Keywords provided by Lund University Hospital:
Lymphoma
Diffuse large B-cell lymphoma
Valproate
R-CHOP
CD 20

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Cyclophosphamide
Rituximab
Doxorubicin
Prednisone
Vincristine
Valproic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on August 23, 2016