Additional identifiers
EudraCT number
2009-011078-14
ClinicalTrials.gov number
Protocol/serial number
7344
Study information
Scientific title
A single arm phase II study to investigate the use of Lenalidomide in the treatment of patients with early stage chronic lymphocytic leukaemia (CLL) associated with poor prognostic factors
Acronym
RESPeCT
Study hypothesis
The majority of patients with chronic lymphocytic leukaemia (CLL) are diagnosed with early stage disease (Binet stage A or Rai stage 0/I). Standard management of such patients is observation, and with median age at diagnosis of 72 and median time to progression of greater than 5 - 10 years, many will never require treatment. In contrast, a proportion of patients have more aggressive disease, and over the last decade, a number of molecular factors have been identified that may be used to identify patients with poor prognosis disease. Each is associated with shortened time to treatment (typically less than 3 years in patients with two or more factors), reduced survival, with in the case of p53/ATM inactivation, resistance to treatment.
Whether it is possible to improve the outcome of patients with CLL and adverse prognostic factors by early intervention with treatment is unknown. Several trials in the 1980's demonstrated that treatment of stage A CLL with conventional chemotherapy (chlorambucil) did not alter the natural history of the disease, although none of these studies stratified patients according to risk. The choice of alternative potential therapeutic agents is limited; they should be effective in patients with adverse prognostic factors, have acceptable toxicity, be able to overcome the drug resistance associated with p53/ATM inactivation and ideally be orally administered.
Two recent phase II trials have demonstrated that Lenalidomide is effective in the treatment of relapsed/refractory disease. Importantly, both studies included a high proportion of patients with adverse prognostic factors including p53 inactivation. The principle objective of this study is to investigate the efficacy of Lenalidomide in achieving disease response (complete remission and clearance of minimal residual disease) in patients with poor risk early stage disease, together with assessment of safety and tolerability.
As of 02/05/2012, the anticipated end date of trial has been updated from 01/04/2012 to 24/11/2011.
Ethics approval
North West 7 Research Ethics Committee approved on the 27th November 2009 (ref: 09/H1008/122)
Study design
Non-randomised multicentre interventional treatment trial
Primary study design
Interventional
Secondary study design
Non randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (chronic)
Intervention
Oral lenalidomide at escalating dose for 3 x 28 day cycles (2.5 mg daily, 5 mg daily, 10 mg daily), then maintenance phase at 10 mg (or maximum tolerated dose).
Intervention type
Drug
Phase
Phase II
Drug names
Lenalidomide
Primary outcome measures
Complete remission with clearance of minimal residual disease (MRD). Response to treatment to be assessed continually, with a more detailed assessment after 6 months of treatment (or earlier if clinically indicated). For patients in complete remission clearance of MRD is assessed every 6 months.
Secondary outcome measures
1. Safety and tolerability of treatment, assessed continually throughout treatment by collection of adverse event data, blood results, etc.
2. Event free survival, assessed each time patients are seen - at least once per month during treatment with study drug and then annually once off study drug and in long-term follow-up
3. Time to next treatment, assessed each time patients are seen - at least once per month during treatment with study drug and then annually once off study drug and in long-term follow-up
Overall trial start date
01/04/2010
Overall trial end date
24/11/2011
Reason abandoned
Eligibility
Participant inclusion criteria
1. Binet stage A CLL
2. Two or more risk factors:
2.1. Unmutated IgVH locus (=98% homology to germline sequence)
2.2. CD38 expression (greater than 7%)
2.3. Deletion of chromosome 11q22 (greater than 20% by FISH)
2.4. Deletion of chromosome 17p13 (greater than 10% by FISH)
3. Over 18 years old, either sex
4. Capable to provide written informed consent
5. Eastern Cooperative Oncology Group (ECOG) performance status less than 2
6. Life expectancy greater than 2 years
7. Must agree to not share study lenalidomide with someone else
8. Must agree not to donate blood whilst taking the study drug and for one week after discontinuation of treatment
9. Female subjects of child bearing potential and all male subjects must agree to comply with the stipulations of the pregnancy prevention plan
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 40; UK Sample Size: 40
Participant exclusion criteria
1. Current or recent (within the last 1 month) participation in another clinical trial investigation the action of an investigational medicinal product for the treatment of CLL
2. Pregnant or lactating
3. Known positivity for human immunodeficiency virus (HIV) types 1 or 2
4. Prior history of malignancies, other than CLL, unless the subject was treated with curative intent and has been free of the disease for 3 years. Exceptions include the following:
4.1. Basal cell carcinoma of the skin
4.2. Squamous cell carcinoma of the skin
4.3. Carcinoma in situ of the cervix
4.4. Carcinoma in situ of the breast
5. Significantly abnormal renal or hepatic function:
5.1. Creatinine clearance less than 60 ml/min (measured or calculated)
5.2. Serum aspartate aminotransferase (AST) greater than 3 x upper limit of normal (ULN)
5.3. Serum bilirubin greater than 34 µmol/l
6. Laboratory tumour lysis syndrome according to the Cairo-Bishop classification. Subjects may be enrolled when these abnormalities have been corrected.
7. Peripheral neuropathy (grade = 2)
8. Previous treatment for CLL
9. Previous treatment with Thalidomide or immunomodulatory derivative drugs (including lenalidomide)
10. Treatment with corticosteroids (for CLL or other indications) less than 28 days from study entry
11. Evidence of Richter's transformation
12. Unsupported absolute neutrophil count less than 1 x 10^9/l or platelet count less than 50 x 10^9/l not due to CLL
13. Active autoimmune haemolytic anaemia or thrombocytopenia
14. Any other medical or psychological condition that in the view of the investigator would be likely to impact compliance with the protocol or interfere with trial treatment
Recruitment start date
01/04/2010
Recruitment end date
24/11/2011
Locations
Countries of recruitment
United Kingdom
Trial participating centre
The Christie NHS Foundation Trust
550 Wilmslow Road
Manchester
M20 4BX
United Kingdom
Sponsor information
Organisation
Christie NHS Foundation Trust (UK)
Sponsor details
Wilmslow Road
Manchester
M20 4BX
United Kingdom
Sponsor type
Government
Website
Funders
Funder type
Industry
Funder name
Celgene International Sàrl (Switzerland)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Leukaemia Research Fund (LRF) (UK)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary