Revlimid® Early Stage Poor prognosis Chronic lymphocytic leukaemia (CLL) Trial

ISRCTN	ISRCTN84606869
DOI	https://doi.org/10.1186/ISRCTN84606869
Clinical Trials Information System (CTIS)	2009-011078-14
Protocol serial number	7344
Sponsor	Christie NHS Foundation Trust (UK)
Funders	Celgene International Sàrl (Switzerland), Leukaemia Research Fund (LRF) (UK)

Submission date: 31/03/2010
Registration date: 31/03/2010
Last edited: 19/05/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Mrs Helen Flight
Scientific

The Christie NHS Foundation Trust
Wilmslow Road
Manchester
M20 4BX
United Kingdom

Study information

Primary study design	Interventional
Study design	Non-randomised multicentre interventional treatment trial
Secondary study design	Non randomised controlled trial
Study type	Participant information sheet
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
Study acronym	RESPeCT
Study objectives	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(s)	North West 7 Research Ethics Committee approved on the 27th November 2009 (ref: 09/H1008/122)
Health condition(s) or problem(s) studied	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 / device / biological / vaccine name(s)	Lenalidomide
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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
Completion date	24/11/2011

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	40
Key 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
Key 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
Date of first enrolment	01/04/2010
Date of final enrolment	24/11/2011

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

The Christie NHS Foundation Trust

550 Wilmslow Road
Manchester
M20 4BX
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan	Not provided at time of registration

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results		04/03/2021	19/05/2022	No	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

19/05/2022: EU Clinical Trials Register results added.
04/03/2016: No publications found, study status unverified