Condition category
Cancer
Date applied
05/03/2014
Date assigned
05/03/2014
Last edited
05/03/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Dr Rachel Blundred

ORCID ID

Contact details

Institute for Cancer Studies
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
r.m.blundred@bham.ac.uk

Additional identifiers

EudraCT number

2012-002795-13

ClinicalTrials.gov number

Protocol/serial number

13956

Study information

Scientific title

Acronym

CyCLLe

Study hypothesis

The CyCLLe trial aims to measure the spontaneous proliferation (growth) rate of leukaemia cells in patients with Chronic Lymphocytic Leukaemia (CLL) and evaluate the effect of an immunosuppressive drug called Cyclosporin A (CsA), on the rate of proliferation.

For the majority of patients, CLL is incurable and once the disease has progressed it can lead to chronic illness, reduced survival and poor quality of life. CLL progression occurs when there is an imbalance between the growth of new leukaemic cells and the rate of cell death. This trial will investigate a strategy for delaying the progression of CLL using CsA.

Activated Tcells appear to perform an important role in tumour cell proliferation. As CsA is known to decrease T cell activation in tumour cells, it is possible it could reduce the rate of growth of new tumour cells and therefore delay disease progression.

The trial will recruit 10 patients with early stage CLL, who do not currently require therapy, from 2 Trials Acceleration Programme (TAP) centres. The research is funded by Leukaemia and Lymphoma research.

The rate of cell growth and loss of cells from the circulation will be assessed over up to 3 cycles (8 weeks apart) using deuterated (heavy) glucose. Patients will attend clinic on day 0 of each cycle to drink a sugar solution containing deuterated glucose and provide a blood sample. Patients will return on day 4 of each cycle for a further blood test to measure proliferation rates. Treatment will begin at week 5 of the first cycle for 8 weeks, continuing for an additional 4 months if a benefit is seen. Patients will be seen once/twice weekly whilst on treatment.

Rates of release may also be measured in patients who consent to additional visits for extra blood samples. The maximum time the patient would be on study is 11 months.

More details can be found at: http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=13956

Ethics approval

12/EE/0485; First MREC approval date 12/12/2012

Study design

Non-randomised; Interventional; Design type: Screening

Primary study design

Interventional

Secondary study design

Non randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (chronic)

Intervention

Cyclosporin A, Immunosuppressant

Follow Up Length: 2 month(s)
Study Entry : Registration only

Intervention type

Drug

Phase

Not Applicable

Drug names

Cyclosporin A

Primary outcome measures

Change in proliferation rate of CLL cells; Timepoint(s): Change in proliferation rate of CLL cells after 4 weeks of CsA therapy, measured by
deuterated glucose

Secondary outcome measures

1. Complete response rate
2. Complete Remission after 8 weeks and 6 months
3. CsA Loss of labelled CLL cells; Timepoint(s): Rate of loss of labelled CLL cells from the circulation with CsA therapy
4. Overall response rate; Timepoint(s): Overall response rate (Complete Remission + Partial Remission) after 8 weeks and 6 months of CsA
5. Release of labelled CLL cells; Timepoint(s): Time to maximum release of labelled CLL cells into the circulation with CsA therapy
6. Spontaneous intra-patient variation; Timepoint(s): Spontaneous intra-patient variation in the proliferation, release and loss of CLL cells from the cirulation
7. Toxicity of CsA in patients with CLL; Timepoint(s): Toxicity of CsA in patients with CLL (toxicities will be measured and graded according to CTCAE criteria

Overall trial start date

29/04/2013

Overall trial end date

29/04/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Stage A or B CLL (Binet system) not requiring therapy by conventional criteria
2. ≤ 2 lines of previous therapy for CLL
3. Male and female, age ≥18
4. ECOG performance status ≤2
5. Life expectancy >12 months
6. No therapy for CLL in previous 3 months (including glucocorticoids)
7. CD38+ve ≥ 7%
8. Normal renal function (eGFR >60mls/min)
9. Normal liver function (AST and / or ALT <1.5 ULN)
10. Negative serology for Hepatitis B, C and HIV
11. Valid informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 10; UK Sample Size: 10

Participant exclusion criteria

1. Active infection
2. Active autoimmune disease (requiring therapy)
3. Diabetes Mellitus
4. Previous myocardial infarction or clinically significant cardiac dysrhythmia.
5. Uncontrolled hypertension
6. Taking medication known to cause serious interaction with CsA where the interaction cannot be prevented by monitoring and adjusting CsA level
7. Fludarabine refractory disease (Non response to or relapse within 6 months of fludarabine containing regimen)
8. Previous bone marrow transplant
9. History of prior malignancy, with the exception of certain skin cancers and malignancies treated with curative intent and with no evidence of active disease for more than 3 years.
10. Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry)
11. Patients and partners of childbearing potential not willing to use effective contraception during and for 3 months after therapy

Recruitment start date

29/04/2013

Recruitment end date

29/04/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Institute for Cancer Studies
Birmingham
B15 2TT
United Kingdom

Sponsor information

Organisation

University of Birmingham (UK)

Sponsor details

Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

University/education

Website

Funders

Funder type

Charity

Funder name

Leukaemia & Lymphoma Research (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