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

Primary Purpose

Chronic Lymphocytic Leukaemia

Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Lenalidomide
Sponsored by
The Christie NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukaemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • The Royal Bournemouth Hospital
  • Heart of England NHS Foundation Trust
  • Addenbrooke's Hospital
  • University Hospital of Wales
  • St James's University Hospital
  • The Royal Liverpool and Broadgreen University Hospital
  • King's College Hospital
  • The Christie NHS Foundation Trust
  • Mid Yorkshire Hospitals NHS Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lenalidomide for early stage poor prognosis CLL

Arm Description

Outcomes

Primary Outcome Measures

Complete Remission with clearance of Minimal Residual Disease (MRD)

Secondary Outcome Measures

Event free survival
Defined as interval from the first treatment day to the first sign of disease progression, treatment for relapse or death (whichever occurs first).
Safety & tolerability of treatment (occurrence of adverse events)
Adverse events will be monitored according to NCI CTCAE v3 from screening until 1 month after treatment discontinuation/ trial closure. Adverse event data will be captured at all visits (6 visits per month in dose escalation, 1 visit per month in dose maintenance). Adverse event data will be assessed by blood tests, physical exam/ vital signs and pregnancy testing.
Time to next treatment
Defined as interval between first treatment day on the study protocol to the first day of the next course of CLL therapy following disease progression.

Full Information

First Posted
May 19, 2010
Last Updated
December 2, 2011
Sponsor
The Christie NHS Foundation Trust
Collaborators
Celgene Corporation, Leukemia Research Fund
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1. Study Identification

Unique Protocol Identification Number
NCT01127542
Brief Title
RESPeCT: Revlimid Early Stage Poor Prognosis Chronic Lymphocytic Leukaemia (CLL) Trial
Acronym
RESPeCT
Official Title
A Single Arm Phase II Study to Investigate the Use of Lenalidomide in the Treatment of Patients With Early Stage CLL Associated With Poor Prognostic Factors
Study Type
Interventional

2. Study Status

Record Verification Date
December 2011
Overall Recruitment Status
Terminated
Why Stopped
Potential safety issue of second primary malignancies in patients treated with lenalidomide.
Study Start Date
May 2010 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
The Christie NHS Foundation Trust
Collaborators
Celgene Corporation, Leukemia Research Fund

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukaemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lenalidomide for early stage poor prognosis CLL
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid, CC-5013
Intervention Description
Daily oral lenalidomide. Starting dose of 2.5mg daily, escalating to target dose of 10mg daily.
Primary Outcome Measure Information:
Title
Complete Remission with clearance of Minimal Residual Disease (MRD)
Time Frame
6 months (or earlier if clinically indicated)
Secondary Outcome Measure Information:
Title
Event free survival
Description
Defined as interval from the first treatment day to the first sign of disease progression, treatment for relapse or death (whichever occurs first).
Time Frame
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)
Title
Safety & tolerability of treatment (occurrence of adverse events)
Description
Adverse events will be monitored according to NCI CTCAE v3 from screening until 1 month after treatment discontinuation/ trial closure. Adverse event data will be captured at all visits (6 visits per month in dose escalation, 1 visit per month in dose maintenance). Adverse event data will be assessed by blood tests, physical exam/ vital signs and pregnancy testing.
Time Frame
Assessed at all visits (6 visits per month in dose escalation, 1 visit per month in dose maintenance, annual in long-term follow-up)
Title
Time to next treatment
Description
Defined as interval between first treatment day on the study protocol to the first day of the next course of CLL therapy following disease progression.
Time Frame
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adrian Bloor
Organizational Affiliation
The Christie NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Royal Bournemouth Hospital
City
Bournemouth
State/Province
Dorset
ZIP/Postal Code
BH7 7DW
Country
United Kingdom
Facility Name
Heart of England NHS Foundation Trust
City
Birmingham
ZIP/Postal Code
B9 5SS
Country
United Kingdom
Facility Name
Addenbrooke's Hospital
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
University Hospital of Wales
City
Cardiff
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Facility Name
St James's University Hospital
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
The Royal Liverpool and Broadgreen University Hospital
City
Liverpool
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Facility Name
King's College Hospital
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
The Christie NHS Foundation Trust
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
Mid Yorkshire Hospitals NHS Trust
City
Wakefield
ZIP/Postal Code
WF1 4DG
Country
United Kingdom

12. IPD Sharing Statement

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

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