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Trial registered on ANZCTR


Registration number
ACTRN12617000231347
Ethics application status
Approved
Date submitted
25/10/2016
Date registered
13/02/2017
Date last updated
13/02/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Efficacy of Slow Tempo Inductions and Maintenance using Low Dose Cytarabine and Thioguanine: Single arm study.
Scientific title
Slow Tempo Inductions and Maintenance using Low Dose Cytarabine and Thioguanine.
Single arm study of combination chemotherapy with cytarabine and thioguanine in patients with AML.
Secondary ID [1] 282767 0
NIL
Universal Trial Number (UTN)
U1111-1145-2018
Trial acronym
STIMULus
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed or Refractory Acute Myeloid Leukaemia 289514 0
Newly diagnosed Acute Myeloid Leukaemia 289515 0
Condition category
Condition code
Cancer 289840 289840 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
New diagnosed Acute Myeloid Leukaemia and Refractory/Relapsed Acute Myeloid Leukaemia
Induction chemotherapy (Day1-35)
Cytarabine 20mg/m2 subcutaneoulsy administered daily, Day 1-21
Thioguanine 40mg/m2 orally administered daily, Day 1-21
PEG-filgrastim 6mg administered subcutaneously on Day 8. When absolute neutrophil <1 x 109/L, then repeat PEG-filgrastim subcutaneously injection every 14 days until neutrophil >1.

Repeat induction chemotherapy if bone marrow (D31-35) demonstrates residual blasts >5%.

Consolidation Chemotherapy (5wk cycles from Day 1-35)
Cytarabine 20mg/m2 subcutaneously administered daily, Day 1-14
Thioguanine 40mg/m2 orally administered daily, Day 1-14
PEG-filgrastim 6mg administered subcutaneously on Day 8. When absolute neutrophil <1 x 109/L.

Consolidation treatment cycle should be repeated a total of 3 x every 35 days (ie. 3 x 5wk cycles)

Maintenance chemotherapy (6 wk cycles from Day 1-42)
Cytarabine 20mg/m2 subcutaneously administered daily, Day 1-14
Thioguanine 40mg/m2 orally administered daily, Day 1-14
Repeat cycle every 42 days (6wk cycles) for a total of 2 years.

Strategies used to ensure individuals adherence to this protocol
Comprehensive patient schedules are provided to each person with detailed explanations.
Intervention code [1] 287437 0
Treatment: Drugs
Comparator / control treatment
Uncontrolled
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289909 0
To assess the complete response (CR or CRi) rate by blood and bone marrow assessment in patients with AML.
Timepoint [1] 289909 0
Response to induction treatment cycle is assess Day25-31 with a bone marrow biopsy. If the bone marrow demonstrates a Complete remission or incomplete Complete remission, the patient will proceed to consolidation, otherwise the patient will receive a further cycle of induction.
Secondary outcome [1] 328705 0
To examine the safety and tolerability of cytarabine and thioguanine administered over a prolonged treatment schedule in AML patients. This will be determined by documenting adverse events (AEs) by type, frequency, severity and timing with respect to cytotoxic drug administration.
Timepoint [1] 328705 0
During Induction subjects are reviewed weekly for safety and tolerability. Events which delays/interrupts treatment is noted at these visits.
During Consolidation Phase subjects are reviewed on a fortnightly basis for safety and tolerability.
During Maintenance, subjects are reviewed 3 weekly.
Secondary outcome [2] 328706 0
To measure leukaemia free survival (LFS) in this cohort of patients with a high risk of leukaemia relapse, by bone marrow and blood tests. This outcome is assessed at specific timepoints throughout the protocol ie. day 25-31 during Induction, at the end of consolidation phase (day15-35) in cycle 1 and 3 and every 6 wks during the Maintenance phase.
Timepoint [2] 328706 0
This outcome is assessed at specific timepoints throughout the protocol ie. day 25-31 during Induction, at the end of consolidation phase (day15-35) in cycle 1 and 3 and every 6 wks during the Maintenance phase.
Secondary outcome [3] 328707 0
To measure overall survival (OS) in this cohort of patients with a poor prognosis.
Timepoint [3] 328707 0
Review at 2 years post commencement of treatment.

Eligibility
Key inclusion criteria
1. Acute Myeloid leukaemia (based on WHO diagnostic criteria) with:
a. Newly diagnosed AML with age >65yrs, or co-morbidities that are a contraindication to induction chemotherapy (that is, in the view of the treating physician, medically unsuitable for high dose chemotherapy treatment)
b. Untreated Secondary AML or transformed AML, 18 years or above.
c. Relapsed or refractory AML and aged >18 years
2. ECOG Performance Status of 0-2
3. Life expectancy of at least 3 months in relation to diseases other than AML
4. If of child-bearing/fathering potential, agreeable to use permanent contraception (by oral or implantable hormones or double-barrier methods)
5. Able to understand study risk and benefits, and to give informed consent
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Serious hepatic disease (with serum transaminases >5x ULN)
2. Serious renal disease (with serum creatinine >300mmol/L)
3. Other co-morbidity, likely in the investigator's opinion to interfere with participation.
4. Likely inability to comply with treatment and monitoring in the investigator's opinion.
5. Existing or planned pregnancy or lactation.
6. Participation in any concurrent investigational therapeutic study.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
This study will be conducted as a Simon-2-part Phase II trial. the response rate for the null hypothesis is set at 5% and the alternative at 25%. the type I error of this early stopping rule is 0.05 and the average sample number if the null hypothesis is true is 16.8.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 6861 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 14530 0
2065 - St Leonards
Recruitment postcode(s) [2] 14531 0
2065 - Crows Nest

Funding & Sponsors
Funding source category [1] 294777 0
Government body
Name [1] 294777 0
Northern Sydney Local Health District
Address [1] 294777 0
Northern Sydney local Health District
Executive Unit, Building 51, Level 1, Southern Campus
Royal North Shore Hospital, Pacific Highway
St Leonards
NSW 2065
Country [1] 294777 0
Australia
Primary sponsor type
Government body
Name
Northern Sydney local Health District
Address
Northern Sydney local Health District
Executive Unit, Building 51, Level 1, Southern Campus
Royal North Shore Hospital, Pacific Highway
St Leonards
NSW 2065
Country
Australia
Secondary sponsor category [1] 293624 0
None
Name [1] 293624 0
Address [1] 293624 0
Country [1] 293624 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296185 0
Human Research Ethics Committee of Northern Sydney Central Coast Health (EC00132)
Ethics committee address [1] 296185 0
Research Office
Kolling Building, Level 13
Royal North Shore Hospital
St Leonards
NSW 2065
Ethics committee country [1] 296185 0
Australia
Date submitted for ethics approval [1] 296185 0
03/04/2012
Approval date [1] 296185 0
21/08/2012
Ethics approval number [1] 296185 0
1202-064M

Summary
Brief summary
The primary purpose of this trial is to evaluate the efficacy and tolerability of a 'slow tempo' chemotherapy regimen for the treatment of acute myeloid leukaemia (AML).

Who is it for?
You may be eligible to take part in this trial if you have newly diagnosed AML and are aged 65 or over, or are unable to undergo standard care chemotherapy; if you have untreated secondary AML or transformed AML and are aged 18yrs or over; or if you have relapsed or refractory AML are you are aged 18 or over.

Study details
All participants enrolled in this trial will undergo the slow tempo chemotherapy treatment regimen, which will involve 35-day cycles of induction chemotherapy until remission is achieved, followed by three 35-day cycles of consolidation chemotherapy, lastly followed by 42-day chemotherapy cycles for two years. Participants will be assessed for disease progression and for treatment side effects throughout the treatment.

It is hoped that the findings from this trial will provide information on whether slow tempo chemotherapy with low dose cytarabine and thioguanine is safe, tolerable and effective in the treatment of newly diagnosed and refractory/relapsed AML.






Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41154 0
Dr Chris Arthur
Address 41154 0
Haematology Department
Level 5, Acute Services Building
Royal North Shore Hospital
St Leonards
NSW 2065
Country 41154 0
Australia
Phone 41154 0
+61 2 9926 4377
Fax 41154 0
+61 2 9926 4070
Email 41154 0
Chris.Arthur@health.nsw.gov.au
Contact person for public queries
Name 41155 0
Ms Vicki Katsioulas
Address 41155 0
Haematology Department - Clinical Trials
Level 5, Acute Services Building
Royal North Shore Hospital
St Leonards
NSW 2065
Country 41155 0
Australia
Phone 41155 0
+61 2 9926 4175
Fax 41155 0
+61 2 9926 4070
Email 41155 0
Vicki.Katsioulas@health.nsw.gov.au
Contact person for scientific queries
Name 41156 0
Dr William Stevenson
Address 41156 0
Haematology Department
Level 5, Acute Services Building
Royal North Shore Hospital
St Leonards
NSW 2065
Country 41156 0
Australia
Phone 41156 0
+61 2 9926 4377
Fax 41156 0
+61 2 9926 4070
Email 41156 0
William.Stevenson@health.nsw.gov.au

No information has been provided regarding IPD availability
Summary results
No Results