A phase II trial of Cyclosporin A in early adverse risk Chronic Lymphocytic Leukaemia (CLL)

ISRCTN ISRCTN61297219
DOI https://doi.org/10.1186/ISRCTN61297219
Clinical Trials Information System (CTIS) 2012-002795-13
Protocol serial number 13956
Sponsor University of Birmingham (UK)
Funder Leukaemia and Lymphoma Research
Submission date
05/03/2014
Registration date
05/03/2014
Last edited
21/06/2019
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

http://www.cancerresearchuk.org/cancer-help/trials/a-trial-of-cyclosporin-a-for-chronic-lymphocytic-leukaemia-cyclle

Contact information

Dr Rachel Blundred
Scientific

Institute for Cancer Studies
University of Birmingham, Edgbaston
Birmingham
B15 2TT
United Kingdom

r.m.blundred@bham.ac.uk

Study information

Primary study designInterventional
Study designNon-randomised; Interventional; Design type: Screening
Secondary study designNon randomised study
Study type Participant information sheet
Scientific titleA phase II trial of Cyclosporin A in early adverse risk Chronic Lymphocytic Leukaemia (CLL)
Study acronymCyCLLe
Study objectivesThe 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.
Ethics approval(s)12/EE/0485; First MREC approval date 12/12/2012
Health condition(s) or problem(s) studiedTopic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Leukaemia (chronic)
InterventionCyclosporin A, Immunosuppressant

Follow Up Length: 2 month(s)
Study Entry : Registration only
Intervention typeDrug
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Cyclosporin A
Primary outcome measure(s)

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

Key secondary outcome measure(s)

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

Completion date29/04/2015

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexAll
Target sample size at registration10
Total final enrolment5
Key inclusion criteria1. 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
Key exclusion criteria1. 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
Date of first enrolment29/04/2013
Date of final enrolment29/04/2015

Locations

Countries of recruitment

  • United Kingdom
  • England

Study participating centre

Institute for Cancer Studies
Birmingham
B15 2TT
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Basic results 21/06/2019 No No
HRA research summary 28/06/2023 No No
Participant information sheet Participant information sheet 11/11/2025 11/11/2025 No Yes

Editorial Notes

21/06/2019: Added clinicaltrialsregister.eu link to basic results (scientific). Added total final enrollment.
06/07/2017: No publications found, verifying study status with principal investigator.

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