Condition category
Cancer
Date applied
12/03/2008
Date assigned
09/05/2008
Last edited
27/01/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Peter Hillmen

ORCID ID

Contact details

Department of Haematology
Level 3 Bexley Wing
St James's University Hospital
Beckett Street
Leeds
LS9 7TF
United Kingdom
-
peter.hillmen@nhs.net

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HM07/8281

Study information

Scientific title

CLL8: a randomised, phase III study to assess alemtuzumab consolidation therapy in patients with Chronic Lymphocytic Leukaemia (CLL) who have responded to previous therapy

Acronym

CLL8

Study hypothesis

The trial is intended to assess the effect on progression free survival (PFS) of subcutaneous alemtuzumab in B-cell chronic lymphocytic leukaemia (B-CLL) patients who have responded to previous chemotherapy.

Ethics approval

Ethics approval pending as of 12/03/2008

Study design

Phase III multi-centre randomised controlled open parallel-group trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Chronic lymphocytic leukaemia (CLL)

Intervention

The recruitment target requires that approximately 96 patients are recruited into the trial per year over a three year period (total = 288).

Prior to randomisation a blood and bone marrow sample will be taken from the patient to measure the level of disease. Patients will then be randomised to receive consolidation therapy with alemtuzumab for 6 - 12 weeks or no consolidation therapy. Both minimal residual disease (MRD) negative and MRD positive patients are eligible for the trial.

Patients randomised to no consolidation therapy will not receive any treatment.

Patients randomised to consolidation therapy with alemtuzumab will receive 30 mg subcutaneous infusion three times a week for six weeks. After six weeks of treatment patients will undergo an assessment of response which will include a further blood sample being taken and a bone marrow sample for those patients who were MRD positive at randomisation. Patients who are assessed as having no detectable CLL (MRD negative) after six weeks of treatment will receive no further treatment with alemtuzumab. Patients who are assessed as having detectable CLL (MRD positive) but showing no improvement will also stop treatment. Patients who are assessed as having detectable CLL (MRD positive) with a reduction in levels after six weeks of treatment will receive a further six weeks of treatment with alemtuzumab. Again such patients will receive 30 mg subcutaneous infusion three times a week for six weeks. Patients will then be assessed for response at the end of treatment which will include a blood and bone marrow sample being taken.

All patients, including those randomised to no consolidation therapy, will then be assessed for a response six months post-randomisation (this assessment can be omitted if within four weeks of the end of treatment assessment in patients who received 12 weeks of treatment with alemtuzumab). All patients will be assessed clinically and with peripheral blood for MRD every three months for three years, although follow up data will only be collected annually. Patients will continue to be followed up annually for survival.

Intervention type

Drug

Phase

Phase III

Drug names

Alemtuzumab

Primary outcome measures

Progression free survival (PFS).

Secondary outcome measures

1. Proportion of patients with undetectable minimal residual disease (MRD), measured at the six month post-randomisation follow-up visit
2. Response as measured by National Cancer Institute (NCI)/International Workshop on CLL (IWCLL) criteria:
2.1. For patients receiving treatment with alemtuzumab: after six weeks of treatment (and 12 weeks if applicable)
2.2. For patients not receiving treatment with alemtuzumab: three months post-randomisation
2.3. For all patients: six months after randomisation (omitted if within four weeks of prior assessment) and 12 months after randomisation
3. Overall survival (OS)
4. Time to MRD relapse for patients who are or who become MRD negative
5. Safety and toxicity: measured from consent until 30 days after the last day of the last treatment with alemtuzumab for patients receiving treatment, and until six months after randomisation for patients not receiving treatment with alemtuzumab
6. Quality of life: measured at baseline and 3, 6, 12, 24 and 36 months after randomisation
7. Quality adjusted life years (QALYs)

Please note that the timepoints above only refer to the proportion of patients with undetectable MRD at the six-month post-randomisation follow-up visit, response, safety and quality of life as the other outcomes are not measured at specific time points.

Overall trial start date

01/06/2008

Overall trial end date

01/12/2014

Reason abandoned

Eligibility

Participant inclusion criteria

1. At least 18 years old, either sex
2. Previous confirmation of B-CLL with a characteristic immunophenotype on peripheral blood flow cytometry
3. Maximum of three prior therapies received for CLL treatment
4. Between 6 and 12 months since completing most recent therapy for CLL
5. Response to most recent chemotherapy treatment for CLL with partial response (PR), near complete response (nCR) or complete response (CR)
6. No prior alemtuzumab therapy
7. Absence of clinically evident lymphadenopathy (largest lymph node less than 2 cm in minimum diameter)
8. Creatinine and bilirubin less than two times upper limit of normal
9. Peripheral B-cell count less than 5 x 10^9 l
10. Written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

96 patients per year over a three year period (total = 288)

Participant exclusion criteria

1. Disease progression after response to latest therapy
2. Active infection
3. Past history of anaphylaxis following exposure to rat or mouse derived complementarity determining region (CDR)-grafted humanised monoclonal antibodies
4. Pregnancy, lactation or women of child-bearing potential unwilling to use medically approved contraception whilst receiving treatment
5. Men whose partners are capable of having children but who are not willing to use appropriate medically approved contraception during the study, unless they are surgically sterile
6. Central nervous system (CNS) involvement with CLL
7. Mantle cell lymphoma
8. Other severe, concurrent diseases or mental disorders
9. Known human immunodeficiency virus (HIV) positive
10. Active secondary malignancy
11. Persisting severe pancytopenia (neutrophils less than 0.5 x 10^9/l or platelets less than 50 x 10^9/l)
12. Patients previously treated with allogeneic stem cell transplantation (SCT)

Recruitment start date

01/06/2008

Recruitment end date

01/12/2014

Locations

Countries of recruitment

United Kingdom

Trial participating centre

St James's University Hospital
Leeds
LS9 7TF
United Kingdom

Sponsor information

Organisation

Leeds Teaching Hospitals NHS Trust (UK)

Sponsor details

Research and Development
Floor A/B - Old Site
Leeds General Infirmary
Great George Street
Leeds
LS1 3EX
United Kingdom

Sponsor type

Government

Website

http://www.leedsteachinghospitals.com/

Funders

Funder type

Industry

Funder name

Bayer Schering Pharma (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

Publication citations

Additional files

Editorial Notes