Clinical trial NCT02144623: Pretreatment With Valproate Prior to Immunotherapy Targeting Cluster of Differentiation Antigen 20 in Chronic Lymphocytic Leukemia
Official title: Pretreatment With Valproate Prior to Immunotherapy Targeting Cluster of Differentiation Antigen 20 in Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Chronic Lymphocytic Leukemia
Keywords: Chronic Lymphocytic Leukemia
Valproate
Cluster of differentiation antigen 20
Lymphomas
B-cell lymphomas
Translational research
Monoclonal antibodies
Lead sponsor: Lund University Hospital
Sponsor class: OTHER
First posted: 2014-05-22
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Levels of CD20 protein and messengerRNA in response to treatment with valproate in patients with chronic lymphatic leukemia.
timeFrame: 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 outcomes:
measure: Translational blood samples.
timeFrame: 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 outcomes:
measure: Number of patients with adverse events as a measure of safety and tolerability.
timeFrame: During treatment period (6 weeks) and 4 weeks post treatment, in total 10 weeks.
Locations:
city: Lund
country: Sweden
facility: Lund University Hospital, Department of Oncology
Study officials:
affiliation: Lund University Hospital
name: Kristina Drott, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: