Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12608000495325
Ethics application status
Approved
Date submitted
13/08/2008
Date registered
30/09/2008
Date last updated
13/11/2018
Date data sharing statement initially provided
13/11/2018
Date results provided
13/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
R3: An International Collaborative Trial for Relapsed and Refractory Acute Lymphoblastic Leukaemia (ALL)
Scientific title
The analysis of survival rates in R3: An International Collaborative Trial for Relapsed and Refractory Acute Lymphoblastic Leukaemia (ALL) to improve treatment results for children with relapsed or resistant leukaemia by using chemotherapy and radiotherapy based on Minimal Residual Disease monitoring
Secondary ID [1] 680 0
ISCRTN number for ALLR3 45724312. University Hospitals of Leicester NHS Trust
Universal Trial Number (UTN)
Trial acronym
ALL_R3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
relapsed acute lymphoblastic leukaemia in children 3551 0
Condition category
Condition code
Cancer 3707 3707 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
multi-agent chemotherapy, based on early response as measured by minimal residual disease (MRD) levels

Phase I Induction (weeks 1-4):
Intrathecal Methotrexate, <2yrs 8mg; 2yrs 10mg; >3 yrs 12mg, on day 1,of week 1 and day 1 of Week 2.
Idarubicin or Mitoxantrone, 10mg/m2 intravenous (IV) over 1 hour, on days 1 and 2 of week 1.
Dexamethasone, 20mg/m2 orally in 2 divided doses per day (max 40mg/day), on days 1-5 of week 1 and days 1-5 of week 3.
Vincristine, 1.5mg/m2 iv bolus (max 2mg as a single dose), on day 3, week 1, day 3 of week 2, day 3 of week 3, day 3 of week 4.
Peg Asparaginase, 1000u/m2 intramuscular(im), on day 3 of week 1 and day 3 of week 3 OR Erwinase, 20,000units/m2 (im) on day 3 of week 1 and then alternate days for 12 doses in total.

Phase II Consolidation (weeks 5-8):
Dexamethasone, 6mg/m2 orally in 2 divided doses, on days 1-5 of week 5.
Vincristine, 1.5mg/m2 (iv), Max 2mg as a single dose, on day 3 of week 5.
Intrathecal Methotrexate, <2yrs 8mg; 2 yrs 10mg; >3 yrs 12mg, on day 1 of week 6
Methotrexate, 1000mg/m2 (iv) over 36 hours, on day 1 of week 6
Peg Asparaginase, 1000u/m2, (im) on day 2 of week 6, 4 hours after the end of methotrexate infusion. OR if allergic to E. Coli Asparaginase
Erwinase, 20,000u/m2 (im), on day 2 of week 6, 4 hours after end of MTX infusion and then alternate days for 6 doses in total
Cyclophosphamide, 440mg/m2 (iv) infusion over 30 minutes, on day 1-5 of week 7
Etoposide, 100mg/m2 (iv) over 4 hours, on days 1-5 of week 7.

Phase III Intensification (weeks 9-13)
Dexamethasone, 6mg/m2 orally in 2 divided doses, on days 1-5 of week 9.
Vincristine, 1.5mg/m2 (iv), Max 2mg as a single dose, on day 3 of Week 9
Intrathecal Methotrexate, <2yrs 8mg; 2yrs 10mg; >3yrs 12mg, on day 1 of week 9.
Cytarabine, 3000mg/m2 (iv) over 3 hours, every 12 hours, on day 1 and 2 of week 9 and day 1, 2 of week 10.
Erwinase, 20,000u/m2 (im), on day 2 and day 4 of week 9 and on day 2 and day 4 of week 10.
Prednisolone eye drops every 2 hours from day 1, week 9 and stopped 5 days after the last Cytarabine infusion.
Intrathecal Methotrexate, <2yrs 8mg; 2yrs 10mg; >3yrs 12mg, on day 1 of week 12.
Methotrexate, 1000mg/m2 (iv) over 36 hours, on day 1 of week 12
Erwinase 20,000u/m2 (im), on day 2 of week 12, 4hrs after the end of the Methotrexate infusion.
Intervention code [1] 3264 0
Treatment: Drugs
Comparator / control treatment
none
Control group
Uncontrolled

Outcomes
Primary outcome [1] 4611 0
Evaluate Progression Free Survival (PFS) for all patients, stratified by risk groups. PFS is defined throughout as the time from trial entry to the first occurrence of progression, relapse, death in Complete Clinical Remission (CCR) or second malignancy.
Timepoint [1] 4611 0
Diagnosis, Remission, Relapse or Death or last follow up in remission
Primary outcome [2] 4671 0
Progression Free Survival
Timepoint [2] 4671 0
Diagnosis to first occurrence of progression, relapse or death
Secondary outcome [1] 7780 0
Evaluate whether a Minimal Residual Disease (MRD) level of 10-4 is a suitable criterion at the end of induction, on which to decide whether chemotherapy or stem cell transplantation (SCT) will be most beneficial to patients in the intermediate risk group. The two groups will be compared through statistical methods
Timepoint [1] 7780 0
Diagnosis, end of Induction and Week 13 of treatment

Eligibility
Key inclusion criteria
Inclusion Criteria:
1. All patients aged 1-18 years who have been previously diagnosed to have acute lymphoblastic leukaemia and have either relapsed after treatment or have primary refractory disease
2. Only those patients in whom this is the first relapse are eligible
3. Written, informed consent according to national guidelines
4. Appropriate ethical committee approval.
Minimum age
1 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria:
1. Those who have first relapse but have already received chemotherapy or radiotherapy for the relapse, prior to starting R3
2. Patients who have had a prior bone marrow transplant
3. Those with mature B-cell ALL

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
9/02/2006
Actual
17/11/2006
Date of last participant enrolment
Anticipated
Actual
15/04/2013
Date of last data collection
Anticipated
Actual
31/12/2016
Sample size
Target
300
Accrual to date
Final
354
Recruitment in Australia
Recruitment state(s)
NSW,VIC,QLD,SA,NT,TAS
Recruitment outside Australia
Country [1] 1153 0
United Kingdom
State/province [1] 1153 0

Funding & Sponsors
Funding source category [1] 3730 0
Government body
Name [1] 3730 0
National Health and Medical Research Council (NHMRC) through Clinical Oncology Society of Australia (COSA) / Australian and New Zealand Children's Haematology/Oncology Group (ANZCHOG)
Country [1] 3730 0
Australia
Primary sponsor type
Other Collaborative groups
Name
University Hospitals of Leicester National Health Service (NHS) Trust
Address
Trust Headquarters
Gwendolen House
Gwendolen Road
Leicester LE5 4QF
Country
United Kingdom
Secondary sponsor category [1] 3347 0
Other Collaborative groups
Name [1] 3347 0
Australia New Zealand Childhood Oncology & Haematology Group
Address [1] 3347 0
200 Greenhill Road
EASTWOOD SA 5063
Country [1] 3347 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5783 0
Women's & Children's Hospital Research Ethics committee
Ethics committee address [1] 5783 0
Ethics committee country [1] 5783 0
Australia
Date submitted for ethics approval [1] 5783 0
Approval date [1] 5783 0
09/02/2006
Ethics approval number [1] 5783 0
1789

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28839 0
A/Prof Tamas Revesz
Address 28839 0
Womens' & Children's Hospital, 72 King William Road, Adelaide 5006
Country 28839 0
Australia
Phone 28839 0
+61881617327
Fax 28839 0
Email 28839 0
[email protected]
Contact person for public queries
Name 11996 0
Associate Professor Tamas Revesz
Address 11996 0
Women's and Children's Hospital
72 King William Road
North Adelaide, SA 5006
Country 11996 0
Australia
Phone 11996 0
(08) 8161 7327
Fax 11996 0
(08) 8161 6567
Email 11996 0
[email protected]
Contact person for scientific queries
Name 2924 0
Professor Vaskar Saha
Address 2924 0
Paediatric and Adolescent Oncology Unit
Christie Hospital
Manchester M20 4BX
Country 2924 0
United Kingdom
Phone 2924 0
(+44) 161 446 3094
Fax 2924 0
(+44) 161 446 3092
Email 2924 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual data protection


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.