Condition category
Cancer
Date applied
05/07/2013
Date assigned
05/07/2013
Last edited
26/01/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Mrs Sonia Fox

ORCID ID

Contact details

Edgbaston
Birmingham
B15 2TT
United Kingdom
-
s.fox.2@bham.ac.uk

Additional identifiers

EudraCT number

2013-000341-39

ClinicalTrials.gov number

Protocol/serial number

14761

Study information

Scientific title

A Phase Ib Study of Eltrombopag and Azacitidine in Patients with High Risk Myelodysplastic Syndromes and Related Disorders

Acronym

ELASTIC

Study hypothesis

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

13/SC/0309; First MREC approval date 28/06/2013

Study design

Non-randomised; Interventional; Design type: Treatment

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

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 names

Eltrombopag and Azacitidine

Primary outcome measures

Safety and tolerability of eltrombopag in combination with azacitidine; Timepoint(s): Within 5 weeks (1 cycle) of azacitidine treatment

Secondary outcome measures

1. To establish the Optimal Biological dose (OBD) of eltrombopag in combination with azacitidine; Timepoint(s): Within 5 weeks (1 cycle) of azacitidine treatment
2. To evaluate evidence for a dose response effect of eltrombopag on bone marrow blast percentage; Timepoint(s): During 3 cycles of azacitidine treatment
3. To evaluate the activity of eltrombopag plus azacitidine per IWG 2006 response criteria for MDS; Timepoint(s): During 3 cycles of azacitidine treatment
4. To evaluate the dosage effect of eltrombopag on stem/progenitor subset numbers and fate; Timepoint(s): During 3 cycles of azacitidine treatment
5. To evaluate the effect of eltrombopag on azacitidine treatment delays and dose reductions; Timepoint(s): During 3 cycles of azacitidine treatment
6. To evaluate the effect of eltrombopag on bleeding complications; Timepoint(s): During 3 cycles of azacitidine treatment
7. To evaluate the effect of eltrombopag on platelet counts; Timepoint(s): During 3 cycles of azacitidine treatment
8. To evaluate the effect of eltrombopag on the need for platelet transfusions; Timepoint(s): During 3 cycles of azacitidine treatment

Overall trial start date

02/09/2013

Overall trial end date

05/10/2015

Reason abandoned

Eligibility

Participant 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 [2] or Chronic Myelomonocytic Leukaemia (CMML) with 1029%
bone marrow blasts without proliferation (peripheral white
blood cell count <13 x 109/l)or Acute Myeloid Leukaemia (AML) with 2030%
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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 37; UK Sample Size: 37; Description: As this is a 3+3 design, no formal power calculation has been carried out and analysis will be descriptive only.

Participant 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.

Recruitment start date

02/09/2013

Recruitment end date

05/10/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

University of Birmingham
Birmingham
B15 2TT
United Kingdom

Sponsor information

Organisation

University of Birmingham

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