PREVAIL: Pretreatment With Valproate Prior to Immunotherapy Targeting Cluster of Differentiation Antigen 20 in Chronic Lymphocytic Leukemia

Sponsor

Lund University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT02144623

Collaborator

(none)

Enrollment

Location

Arm

25.2

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial includes patients with chronic lymphocytic leukemia, the most common kind of malignant lymphoma. Monoclonal antibodies directed against cluster of differentiation antigen 20 have improved treatment results in different forms of lymphomas; however in chronic lymphocytic leukemia treatment with monoclonal antibodies is less effective, and it has been suggested that this is depending on a lower expression of the cluster of differentiation antigen 20 protein on the chronic lymphocytic leukemia cells.

Valproate, an anticonvulsant drug, has been shown to increase the cluster of differentiation antigen 20 expression, and the rationale in this study is that an increasement of cluster of differentiation antigen 20 would make treatment with monoclonal antibodies in patients with chronic lymphocytic leukemia more effective.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia	Drug: Valproate	Early Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pretreatment With Valproate Prior to Immunotherapy Targeting Cluster of Differentiation Antigen 20 in Chronic Lymphocytic Leukemia

Study Start Date :

Jan 1, 2015

Actual Primary Completion Date :

Feb 1, 2016

Actual Study Completion Date :

Feb 6, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Valproate	Drug: Valproate

Arm

Intervention/Treatment

Experimental: Valproate

Drug: Valproate

Outcome Measures

Primary Outcome Measures

Levels of CD20 protein and messengerRNA in response to treatment with valproate in patients with chronic lymphatic leukemia. [Blood samples to determine the level of CD20 and messengerRNA are taken day 1 and 4 at each cycle; 3 cycles are given with a cycle length of 21 days. Valproate concentration are taken day 1, 2, 3 and 4 at each cycle.]

Secondary Outcome Measures

Translational blood samples. [Blood tests for translational studies of the epigenetic and transcriptional regulation of the CD20 promotor are taken prestudy, day 1, 2, 3 and 4 at each cycle and 3 months post treatment.]

Other Outcome Measures

Number of patients with adverse events as a measure of safety and tolerability. [During treatment period (6 weeks) and 4 weeks post treatment, in total 10 weeks.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18-80 years
Histologically confirmed chronic lymphocytic leukemia
Leucocyte count more than 20 x 10 9/L
No other simultaneous treatment for lymphoma
No treatment indicated for chronic lymphocytic leukemia
WHO performance status 0-2
HIV negativity
Negativity for hepatitis C virus , HBsAG, anti-hepatitis B core antigen, or other active infection uncontrolled by treatment
Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy
Agree not to share study medication with another person and to return all unused study drug to the investigator
Written informed concent

Exclusion Criteria:

Psychiatric illness or condition which could interfere with the subjects' ability to understand the requirements of the study
Neurological or neuropsychiatric disorder, interfering with the requirements of the study
Hearing impairment over grade 2
Porphyria
History of acute or chronic hepatitis
Family history of severe drug-induced hepatitis
Pregnancy and lactation