CLOfarabine (Clolar®) Used with DaunoXome® in acute myeloid leukaemia

ISRCTN	ISRCTN29644734
DOI	https://doi.org/10.1186/ISRCTN29644734
Secondary identifying numbers	RG_08-016

Submission date: 21/10/2008
Registration date: 05/02/2009
Last edited: 15/03/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English Summary

http://www.cancerhelp.org.uk/trials/trial-clofarabine-and-liposomal-daunorubicin-for-children-and-teenagers-with-acute-myeloid-leukaemia-cloud

Contact information

Dr Pam Kearns
Scientific

Institute of Child Health
4th Floor, Whittal Street
Birmingham
B6 6NH
United Kingdom

Phone	+44 (0)121 333 8238
Email	P.R.Kearns@bham.ac.uk

Study information

Study design	Multicentre prospective non blinded open label phase I dose escalation study
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Phase I escalation study of clofarabine (Clolar®) and liposomal daunorubicin (DaunoXome®) in childhood and adolescent acute myeloid leukaemia
Study acronym	CLOUD
Study hypothesis	To establish the maximum tolerated dose of clofarabine (Clolar®) when used in combination with DaunoXome®. On 01/03/2011 the anticipated end date was changed from 01/06/2010 to 30/06/2011.
Ethics approval(s)	Amended 11/02/2010: West Midlands Research Ethics Committee, 10/02/2009, ref: 08/H1208/36
Condition	Acute myeloid leukaemia
Intervention	The calculation of dosage is based on the patients body surface area. The dose of DaunoXome® is fixed for all cohorts at 60 mg/m^2. DaunoXome® is given intravenously over 2 hours and start 4 hours after the start of Clofarabine (Clolar®) on days 1, 3 and 5. The starting dose of Clofarabine (Clolar®) will be 60% of the recommended single agent dose for the paediatric population. Clofarabine (Clolar®) is given intravenously over 2 hours on days 1, 2, 3, 4 and 5. Dose escalations in subsequent cohorts will approximate 33% increments. The following dose levels will be studied: Level -1: 20 mg/m^2/day x 5 days Level 0: 30 mg/m^2/day/ x 5 days Level 1: 40 mg/m^2/day x 5 days Dose escalation will be capped at 40 mg/m^2/day. Patients will receive a single cycle of treatment and will be followed up until day 42.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase I
Drug / device / biological / vaccine name(s)	Clofarabine (Clolar®), daunorubicin (DaunoXome®)
Primary outcome measure	To establish the maximum tolerated dose of clofarabine (Clolar®) when used in combination with DaunoXome®. The maximum tolerated dose will be defined by the number of dose-limiting toxicities during cycle 1 of therapy.
Secondary outcome measures	1. To characterise the safety and tolerability of the combination of clofarabine (Clolar®) and DaunoXome® including identification of the dose limiting toxicities 2. To document the overall response rate, including complete remission (CR), complete remission with incomplete blood count recovery (CRi) and partial remission (PR) in this population 3. To describe the durability fo response and follow up of these patients, including the number of patients that undergo stem-cell transplant after re-induction with clofarabine (Clolar®) and DaunoXome® Measured as follows: 1. The nature, incidence and severity of the adverse events, collected throughout cycle 1 of therapy 2. Responses measured by bone marrow assessment between day 21 and 42 post first dose of clofarabine (Clolar®) and DaunoXome®
Overall study start date	01/01/2009
Overall study end date	30/06/2011

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	6 Months
Upper age limit	18 Years
Sex	Both
Target number of participants	12 - 18 patients
Participant inclusion criteria	1. Diagnosis of acute myelogenous leukaemia (AML) 2. Patients must be in first relapse within 12 months of initial diagnosis or refractory to induction therapy or be in second or subsequent relapse 3. Patients with refractory AML following induction must be greater than 20% blasts in the bone marrow 4. Age must be between 6 months to less than 18 years old, either sex 5. Karnofsky or Lansky score of greater than 50 6. Patients of childbearing potential must have a negative pregnancy test and agree to use an effective birth control or evidence of post-menopausal status. Post-menopausal status is defined as either radiation-induced oophorectomy with last menses greater than 1 year ago; chemotherapy induced menopause with 1 year interval since last menses. 7. Normal renal function 8. Normal hepatic function 9. Cardiac function defined as: shortening fraction of greater than 29% by echocardiogram left ventricular ejection fraction (LVEF) greater than 58%
Participant exclusion criteria	1. First relapse greater than 1 year from their initial diagnosis of AML 2. Patients whose previous daunorubicin equivalent exposure equals or exceeds 450 mg/m^2 3. Isolated extramedullary leukaemia 4. Symptomatic central nervous system (CNS) involvement 5. Any evidence of severe or uncontrolled systemic conditions 6. Concurrent treatment or administration of any other experimental drug or with any other cancer therapy 7. Patients unable to be regularly followed up 8. Patient with expected non-compliance to toxicity management guidelines
Recruitment start date	01/01/2009
Recruitment end date	30/06/2011

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Institute of Child Health

Birmingham
B6 6NH
United Kingdom

Sponsor information

University of Birmingham (UK)
University/education

Research & Commercial Services
Aitchison Building
Edgbaston
Birmingham
B15 2TT
England
United Kingdom

Website	http://www.bham.ac.uk
"ROR"	https://ror.org/03angcq70

Funders

Funder type

Charity

Leukaemia Research Fund (UK)

No information available

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?
HRA research summary			28/06/2023	No	No

Editorial Notes

15/03/2015: No publications found in PubMed, verifying study status with principal investigator.