A phase II trial of Cyclosporin A in early adverse risk Chronic Lymphocytic Leukaemia (CLL)
| ISRCTN | ISRCTN61297219 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN61297219 |
| EudraCT/CTIS number | 2012-002795-13 |
| Secondary identifying numbers | 13956 |
- 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
Contact information
Dr Rachel Blundred
Scientific
Scientific
Institute for Cancer Studies
University of Birmingham, Edgbaston
Birmingham
B15 2TT
United Kingdom
| r.m.blundred@bham.ac.uk |
Study information
| Study design | Non-randomised; Interventional; Design type: Screening |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | A phase II trial of Cyclosporin A in early adverse risk Chronic Lymphocytic Leukaemia (CLL) |
| Study 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. |
| Ethics approval(s) | 12/EE/0485; First MREC approval date 12/12/2012 |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Cyclosporin A |
| Primary outcome measure | 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 study start date | 29/04/2013 |
| Overall study end date | 29/04/2015 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 10; UK Sample Size: 10 |
| Total final enrolment | 5 |
| 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 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
- England
- United Kingdom
Study participating centre
Institute for Cancer Studies
Birmingham
B15 2TT
United Kingdom
B15 2TT
United Kingdom
Sponsor information
University of Birmingham (UK)
University/education
University/education
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
"ROR" |
https://ror.org/03angcq70 |
|---|
Funders
Funder type
Charity
Leukaemia and Lymphoma Research
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not 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 |
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.
