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

NCT01127542 | Terminated Phase 2 DMC

• 3 other identifiers: 09_DOG06_992009-011078-14ISRCTN
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 9

Brief Summary

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.

Conditions

Chronic Lymphocytic Leukaemia

Outcome Measures

Primary Outcomes (1)

• Complete Remission with clearance of Minimal Residual Disease (MRD)

  6 months (or earlier if clinically indicated)

Secondary Outcomes (3)

• Event free survival

  Treatment/ progression/ death details collected at all visits (6 visits per month in dose escalation, 1 visit per month in dose maintenance, annual in long-term follow-up)

• Safety & tolerability of treatment (occurrence of adverse events)

  Assessed at all visits (6 visits per month in dose escalation, 1 visit per month in dose maintenance, annual in long-term follow-up)

• Time to next treatment

  Treatment details collected at all visits (6 visits per month in dose escalation, 1 visit per month in dose maintenance, annual in long-term follow-up)

Study Arms (1)

Lenalidomide for early stage poor prognosis CLL

EXPERIMENTAL

Drug: Lenalidomide

Interventions

Lenalidomide DRUG

Daily oral lenalidomide. Starting dose of 2.5mg daily, escalating to target dose of 10mg daily.

Also known as: Revlimid, CC-5013

Lenalidomide for early stage poor prognosis CLL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Binet stage A CLL
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead
• Celgene Corporation: collaborator
• Leukemia Research Fund: collaborator

Study Sites (9)

The Royal Bournemouth Hospital

Bournemouth, Dorset, BH7 7DW, United Kingdom

Location

Heart of England NHS Foundation Trust

Birmingham, B9 5SS, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

St James's University Hospital

Leeds, LS9 7TF, United Kingdom

Location

The Royal Liverpool and Broadgreen University Hospital

Liverpool, L7 8XP, United Kingdom

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Mid Yorkshire Hospitals NHS Trust

Wakefield, WF1 4DG, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, B-Cell

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Adrian Bloor

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: May 19, 2010
• First Posted: May 21, 2010
• Study Start: May 1, 2010
• Study Completion: December 1, 2011
• Last Updated: December 5, 2011

Record last verified: 2011-12

Locations

GB (9)