Official Title: “A Randomized Phase II Trial to Determine Whether the Application of Imiquimod Cream to the Vaccination Site Can Improve the Immune Responsiveness to Influenza Vaccination in Patients With Untreated Chronic Lymphocytic Leukemia”

The purpose of the study is to determine whether it is possible to improve the immune response rate to 'flu vaccination in patients with chronic lymphocytic leukaemia (CLL).

Annual flu vaccination is recommended for all patients with CLL because they are known to be susceptible to infections and particularly to chest infections that may occur as a complication of influenza. Protection against 'flu depends on patients having a high level of antibodies against the 'flu virus. Vaccination works by stimulating the immune system and thus boosting the levels of these protective antibodies.

CLL patients have weakened immune systems due to the leukaemia itself but also following chemotherapy. The exact cause of these immune defects is not known. However, CLL patients typically have low antibody levels and their immune cells may not work normally.

Unfortunately, studies have shown that patients with CLL are not very good at making antibodies to 'flu vaccination and as a result protection against flu is not very reliable.

Recent studies have shown that only 15-20 % of CLL patients will achieve a protective antibody level.

Recently a new type of medical cream has been introduced to treat certain skin conditions.

Its name is Imiquimod and it is licensed to treat viral warts in the genital area and a type of skin cancer called basal cell carcinoma. It works by increasing the immune response in the skin. Animal studies have shown that as well as increasing immunity against viruses and cancers, it increases responses to vaccination when applied at the site of vaccination.

In this study we propose to test whether this new medicine can improve the response to the 'flu jab.

Study Type: Interventional

Study Design: Prevention, Randomized, Open Label, Active Control, Factorial Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2009

Trial Summary

68 patients with stage A CLL who have not been treated, and 34 healthy age and sex matched volunteers who fulfil the entry requirements will be identified and invited to take part in this study.

Blood samples will be taken for baseline studies [FBC, U&E, LFT, Immunoglobulins (Igs), haemagglutinin titres] (20 mls) and T cells studies (50 mls to be frozen).If CLL prognostic factors have not already been determined a further 20ml will be taken for these.

Patients will be randomized to either:

Group A Vaccination with current trispecific influenza vaccine Day 1

or

Group B Vaccination with current trispecific influenza vaccine Day 1, together with the application of Imiquimod cream to the vaccination site on day 2 to 6.

Blood samples will be taken on day 0 for haemagglutinin studies (20 ml) and T cells (50ml to be frozen), then on day 7, 14 for T-cell studies (50 ml) and day 28 for haemagglutinin studies (20 ml). During the 28 days that subjects participate in the trial approximately 190 ml will be taken in total.

Antibody and T-cell responses to influenza virus will be assessed and compared between the two patient arms of the study and the control group.

Intervention(s) in this Clinical Trial

• Drug: Imiquimod cream
  • Imiquimod (aldara) 0.5 % cream to site of vaccination on day 2 to 6
• Drug: influenza vaccine
  • trispecific influenza vaccine 0.5 ml subcutaneously

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Group A CLL patients
  • Vaccination with current trispecific influenza vaccine Day 1
• Experimental: Group B CLL patients
  • Vaccination with current trispecific influenza vaccine Day 1, together with the application of Imiquimod cream to the vaccination site on day 2 to 6.
• Active Comparator: Group C volunteers
  • Vaccination with current trispecific influenza vaccine Day 1

Primary Measures

• Immune responses to influenza vaccine in CLL cohorts and healthy age matched controls
  • Time Frame: Dec 2009
    Safety Issue?: Yes

Secondary Measures

• Investigate immune responses and correlate with CLL prognostic markers
  • Time Frame: Dec 2009
    Safety Issue?: No

Inclusion Criteria:

• Untreated stage A CLL patients
• Healthy volunteers

Exclusion Criteria:

• Patients with other malignancies
• Patients receiving corticosteroids or other immunosuppressive drugs
• Patients who have received vaccination against influenza in the past 6 months
• Patients who have had an allergic reaction to a flu shot in the past, or have an allergy to eggs or who previously developed Guillain-Barré syndrome within 6 weeks of getting a flu shot
• Patients failing to give informed consent.
• Patients using homeopathic remedies such as echniaea cream.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: The Royal Bournemouth Hospital

Overall Clinical Trial Officials and Contacts

Helen McCarthy, MBBS PhD Principal Investigator Royal Bournemouth Hospital  

Overall Contact: Helen McCarthy, MBBS PhD 441202 704790 

Information obtained from ClinicalTrials.gov on September 04, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00596336

Study ID Number: Eudract number: 2006-004902-16

ClinicalTrials.gov Identifier: NCT00596336

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency