RESPeCT: Revlimid Early Stage Poor Prognosis Chronic Lymphocytic Leukaemia (CLL) Trial

The Christie NHS Foundation Trust

Status and phase

Terminated

Phase 2

Conditions

Chronic Lymphocytic Leukaemia

Treatments

Drug: Lenalidomide

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01127542

2009-011078-14 (EudraCT Number)

ISRCTN (Registry Identifier)

09_DOG06_99

Details and patient eligibility

About

The majority of patients with 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 >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 2 of 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.

Enrollment

1 patient

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Binet stage A CLL
2 or more risk factors:
Unmutated IgVH locus (≥98% homology to germline sequence)
CD38 expression (>7%)
Deletion of chromosome 11q22 (>20% by FISH)
Deletion of chromosome 17p13 (>10% by FISH)
Over 18 years old
Capable to provide written informed consent
ECOG performance status < 2
Life expectancy > 2 years
Must agree to not share lenalidomide with someone else
Must agree not to donate blood whilst taking the study drug and for one week after discontinuation of treatment.
Female subjects of childbearing potential and all male subjects must agree to comply with the stipulations of the pregnancy prevention plan.

Exclusion criteria

Current or recent (within the last 1 month) participation in another clinical trial investigating the action of an investigational medicinal product for the treatment of CLL
Pregnant or lactating
Known positivity for human immunodeficiency virus (HIV) types 1 or 2
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:
Basal cell carcinoma of the skin
Squamous cell carcinoma of the skin
Carcinoma in situ of the cervix
Carcinoma in situ of the breast
Significantly abnormal renal or hepatic function (creatinine clearance < 60ml/min, serum aspartate aminotransferase (AST) > 3 x upper limit of normal (ULN), serum bilirubin > 34μmol/l)
Laboratory tumour lysis syndrome according to the Cairo-Bishop classification. Subjects may be enrolled when these abnormalities have been corrected.
Peripheral neuropathy (grade ≥ 2)
Previous treatment for CLL
Previous treatment with Thalidomide or immunomodulatory derivative drugs (including Lenalidomide)
Treatment with corticosteroids (for CLL or other indications) < 28 days from study entry
Evidence of Richter's transformation
Unsupported absolute neutrophil count < 1x109/l or platelet count < 50x10*9/l not due to CLL
Active autoimmune haemolytic anaemia or thrombocytopenia
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.