A Phase Ib study of eltrombopag and azacitidine in patients with high risk myelodysplastic syndromes and related disorders
| ISRCTN | ISRCTN05858391 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN05858391 |
| Clinical Trials Information System (CTIS) | 2013-000341-39 |
| Protocol serial number | 14761 |
| Sponsor | University of Birmingham |
| Funder | Leukaemia and Lymphoma Research |
- Submission date
- 05/07/2013
- Registration date
- 05/07/2013
- Last edited
- 21/07/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
Contact information
Scientific
Centre for Clinical Haematology
Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom
| Phone | +44 (0) 121 371 7868 |
|---|---|
| elastic@trials.bham.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Non-randomised; Interventional; Design type: Treatment |
| Secondary study design | Non randomised study |
| Study type | Participant information sheet |
| Scientific title | A Phase Ib study of eltrombopag and azacitidine in patients with high risk myelodysplastic syndromes and related disorders |
| Study acronym | ELASTIC |
| Study objectives | ELASTIC is a 3+3 cohort trial designed to evaluate the Maximum Tolerated Dose (MTD) and Optimal Biological Dose (OBD) of eltrombopag in combination with azacitidine. This trial will recruit patients with IPSS INT-2/high-risk Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukaemia (CMML-2) and Acute Myeloid Leukaemia (AML) with less than 30% blasts. The objectives of the trial are to evaluate the safety and tolerability of the oral thrombopoietin receptor agonist eltrombopag in combination with azacitidine in patients with advanced MDS and establish the Maximum Tolerated Dose (MTD) and Optimum Biological Dose (OBD). The trial will also aim to investigate the effect of eltrombopag with azacitidine on the fate of MDS/AML stem cell progenitors from patients so treated. The feasibility of Leukaemic Stem Cell (LSC) tracking as a marker of response and predictor of treatment failure in future Phase II/III studies will be explored. A maximum of 27 patients will be recruited to the 3+3 dose finding component of the study and a minimum of 3. The number of patients recruited is determined by the maximum dose of 300mg. An additional 10 patients will then be recruited at the MTD to allow a preliminary estimate of activity. A maximum of 37 patients in total will be recruited to this study. |
| Ethics approval(s) | 13/SC/0309; First MREC approval date 28/06/2013 |
| Health condition(s) or problem(s) studied | Topic: National Cancer Research Network; Subtopic: Haematological Oncology; Disease: Miscellaneous |
| Intervention | Azacitidine, Hypomethylating agent used within its licensed indication; Eltrombopag, Thrombopoietin receptor (TpoR) agonist; Follow Up Length: 7 month(s); Study Entry : Registration only |
| Intervention type | Drug |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Eltrombopag, azacitidine |
| Primary outcome measure(s) |
Safety and tolerability of eltrombopag in combination with azacitidine; Timepoint(s): Within 5 weeks (1 cycle) of azacitidine treatment |
| Key secondary outcome measure(s) |
1. To establish the Optimal Biological dose (OBD) of eltrombopag in combination with azacitidine; Timepoint(s): Within 5 weeks (1 cycle) of azacitidine treatment |
| Completion date | 31/08/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | All |
| Target sample size at registration | 37 |
| Total final enrolment | 31 |
| Key inclusion criteria | 1. Age >=16 years of age 2. Platelet count at baseline <150 x 109/l 3. Myelodysplastic Syndromes (MDS) classified as Intermediate 2 risk or high risk according to the International Prognostic Scoring System (IPSS) at registration or Chronic Myelomonocytic Leukaemia (CMML) with 10-29% bone marrow blasts without proliferation (peripheral white blood cell count <13 x 109/l) or Acute Myeloid Leukaemia (AML) with 20-30% bone marrow blast 4. Subjects must have platelet count and platelet transfusion data available over a period of 4 weeks prior to registration 5. A baseline bone marrow examination to evaluate blast percentage, karyotype and assessment of fibrotic change within 8 weeks of registraton 6. Alanine Aminotransferase ALT/Aspartate Aminotransferase (AST) < 3 x upper limit of normal ECOG = 2 7. Valid informed consent Target Gender: Male & Female ; Lower Age Limit 16 years |
| Key exclusion criteria | 1. AML with >30% blasts 2. Known HIV positive 3. Known liver cirrhosis 4. Uncontrolled infection (grade 4 CTCAE v4) 5. Previous exposure to azacitidine 6. Previous exposure to thrombomimetic agents 7. Use of prior investigational agents within 6 weeks 8. Other severe, concurrent diseases or mental disorders 9. Concurrent active or previous malignancy within the last 3 years except controlled, localised prostate cancer on hormone therapy or non-melanoma skin malignancy or cervical carcinoma in situ or completely resected colonic polyps carcinoma in situ 10. Bone marrow fibrosis 11. Clinical evidence of splenomegaly 12. Known hypersensitivity to study drugs or any of their excipients 13. Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry) 14. Females of childbearing potential (i.e. not postmenopausal or surgically sterilised) who are not willing to use adequate methods of contraception to prevent pregnancy or abstain from heterosexual activity for the duration of the trial and for at least 3 months following treatment discontinuation. 15. Male patients who are not willing to use an adequate method of contraception for the duration of the trial treatment if engaged in sexual activity with a female of childbearing potential and for at least 3 months following treatment discontinuation 16. Patients of east Asian ancestry* * Patients will be excluded if either parent is East Asian (such as Chinese, Japanese, Taiwanese or Korean). In previous studies, the pharmacokinetics of eltrombopag in patients of East Asian ancestry differs significantly from the non-East Asian patients. The SPC for eltrombopag recommends patients receive 50% of the recommended dose. As this is a dose finding study, inclusion of these patients may impair an accurate finding of MTD and OBD that could be applied to the UK population. |
| Date of first enrolment | 02/09/2013 |
| Date of final enrolment | 05/10/2015 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
B15 2TT
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The Cancer Research UK Clinical Trials Unit (CRCTU) is committed to responsible and controlled sharing of anonymised clinical trial data with the wider research community to maximise potential patient benefit while protecting the privacy and confidentiality of study participants. A summary of the clinical trial results is already available. Participant data and the associated supporting documentation will typically be available for all CRCTU clinical trials within 6 months after the publication of the outcome measures. Only scientifically sound proposals from appropriately qualified research groups will be considered for data sharing. Data Sharing Requests will be reviewed independently by the CRCTU Directors in discussion with the Chief Investigator and relevant Trial Management Group and due diligence checks will be performed. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Basic results | 23/09/2021 | 20/05/2022 | No | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Plain English results | Cancer Research UK summary of results | 21/07/2022 | No | Yes |
Editorial Notes
21/07/2022: The following changes have been made:
1. The Cancer Research UK lay results summary has been added.
2. The total final enrolment number has been added.
23/06/2022: The following changes have been made:
1. The intention to publish date has been changed from 31/01/2021 to 01/08/2022.
2. The publication and dissemination plan has been added.
3. The individual participant data (IPD) sharing statement has been added and the IPD sharing summary has been changed from to.
20/05/2022: EU Clinical Trials Register results added.
10/07/2020: The overall trial end date has been changed from 30/05/2020 to 31/08/2020.
18/03/2020: The following changes have been made:
1. The overall trial end date has been changed from 29/03/2019 to 30/05/2020.
2. The intention to publish date has been changed from 31/12/2019 to 30/01/2021.
10/04/2019: The scientific contact has been changed from Sonia Fox (s.fox.2@bham.ac.uk) to Becky Bishop (elastic@trials.bham.ac.uk).
09/04/2019: The following changes were made to the trial record:
1. The overall end date was changed from 05/10/2015 to 29/03/2019
2. The intention to publish date was added
14/11/2017: No publications found, verifying study status with principal investigator.
