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Trial registered on ANZCTR


Registration number
ACTRN12618001734257
Ethics application status
Approved
Date submitted
17/10/2018
Date registered
22/10/2018
Date last updated
8/02/2021
Date data sharing statement initially provided
2/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
ALL09 - SUbstitute BLinatumomab to Improve Minimal Residual Disease Eradication in Adolescents and Young Adults with Acute Lymphoblastic Leukaemia – The SUBLIME Study
Scientific title
ALL09 - Phase II Study of Blinatumomab as Induction Therapy in Adolescent and Young Adult Acute Lymphoblastic Leukaemia
Secondary ID [1] 296359 0
ALL09
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukaemia 310087 0
Condition category
Condition code
Cancer 308835 308835 0 0
Leukaemia - Acute leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
blinatumomab 28mcg/m^2 administered intravenously via an ambulatory infusion device. Dose is administered continuously, as the infusion device is taken home with the patient. The patient will require minimal instruction on the use of the infusion device, as it is programmed and monitored by the nursing staff. Digital data is captured to track dose compliance in the ambulatory setting. Blinatumomab is administered continuously over 2 x 28 day cycles, first during induction and second during the consolidation treatment, representing a 2 month gap between blinatumomab cycles. Standard of care treatment is provided outside of these 2 28-day cycles. Standard of care in this trial is the approved BFM-2000 adapted pediatric protocol currently used in centres in Australia.
Intervention code [1] 312689 0
Treatment: Drugs
Comparator / control treatment
The historical control group is the ALLG ALL06 cohort (15-40 Y/O ALL patients treated with an intensive pediatric protocol including risk stratification).

This trial recruited from 2012 - 2018. Data collection is ongoing until 2022.
Control group
Historical

Outcomes
Primary outcome [1] 307805 0
To assess the rate of minimal residual disease (MRD) negativity, where MRD negativity is defined as no presence of leukaemic blasts in blood or bone marrow sample as determined by EuroMRD accredited q-pcr analysis
Timepoint [1] 307805 0
day 79 of therapy
Secondary outcome [1] 352981 0
Rates of Disease Free Survival measured from the date on which remission (defined by National Comprehensive Cancer Network guidelines) is first documented until the date of relapse (defined by NCCN guidelines) or the date of death, for those patients who die in remission.
Timepoint [1] 352981 0
Time of relapse, death or censor date (minimum 2 years follow up from end of treatment)
Secondary outcome [2] 391607 0
Evaluation toxicity, both haematologic and non-haematologic in comparison to previous ALL6 cohort. This is a composite secondary outcome. This outcome will be assessed by collecting toxicity data throughout treatment from the patients medical records e.g. hospital admissions, blood tests showing haematological abnormalities etc and patient reported outcomes e.g. headaches, fatigue etc.
Timepoint [2] 391607 0
After a minimum of 2 years of follow up from end of treatment.
Secondary outcome [3] 391608 0
Assessment of proportion of patients able to commence protocol M at day 94 when compared to the previous ALL06 cohort. Patients treatment data will be collected in the study electronic data capture system (EDC). This information will be collated from the patients medical records and from pharmacy dispensing records. The date the patient starts treatment will be considered day 1, the proportion of patients who reach protocol M treatment (defined as commencing therapy in the protocol M blocks) by day 94 will be assessed against the ALL06 cohort.
Timepoint [3] 391608 0
After a minimum of 2 years of follow up from end of treatment.
Secondary outcome [4] 391609 0
Assessment of proportion of patients with standard, medium, medium high, high, very high-risk disease compared to the previous ALL06 cohort. This is a composite endpoint. Patients will be stratified in one of 5 risk categories, the proportion of patients in each group will be compared against the previous ALL06 cohort.
Timepoint [4] 391609 0
After a minimum of 2 years of follow up from end of treatment.
Secondary outcome [5] 391610 0
Conducting correlative laboratory scientific studies in blood and bone marrow samples taken from patients enrolled on this study. This is a composite outcome, blood and bone marrow samples will be taken from patients on the trial and analysed.
Timepoint [5] 391610 0
After a minimum of 2 years of follow up from end of treatment.
Secondary outcome [6] 391611 0
Assessment of impact of treatment on physical, functional, and social wellbeing via HRQOL assessments at beginning and end of each phase of treatment and compare with the previous ALL06 cohort. This is a composite outcome which is assessed from patient report outcomes (i.e. the quality of life assessment tool). The QOL questions have been assembled from the Functional Assessment of Chronic Illness Therapy (FACIT) suite.
Timepoint [6] 391611 0
This will be assessed at the beginning of each phase of treatment up until treatment ceases and will be analysed after the last patient recruited has a minimum of 2 years of follow up from end of treatment.
Secondary outcome [7] 391612 0
To provide an indication of fertility status after treatment and compare fertility outcomes to the ALL06 cohort. Fertility assessments are performed specifically for the trial. Patients will be requested to undergo blood and (if applicable) semen testing to determine fertility status. This will be reported on the electronic data capture system.
Timepoint [7] 391612 0
After a minimum of 2 years of follow up from end of treatment.

Eligibility
Key inclusion criteria
1. A morphological diagnosis of B-lineage ALL by WHO criteria. All clinico-pathological sub-types will be eligible, except for mature B or Burkitt ALL;
2. Bone marrow blast count greater than or equal to 20%;
3. Adequate renal and hepatic function at Screening as defined by:
a. Total bilirubin less than 2.5 x ULN unless medically correctable
b. Serum creatinine less than or equal to 200 micromol/L unless medically correctable
4. Normal left ventricular ejection fraction, according to institutional criteria;
5. An ECOG performance status score of 0-3 at Screening.
Minimum age
15 Years
Maximum age
40 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. A diagnosis of T-lineage ALL by WHO criteria.
2. Patients known to have Philadelphia chromosome positive disease as defined by WHO criteria using standard karyotype and/or fluorescence in situ hybridization (FISH) analysis and/or BCR-ABL1 fusion transcript detection
3. Subjects aged less than 15 or more than 40 years at Screening;
4. Presence of serious cardiac, pulmonary, hepatic or renal disease;
5. Previous treatment for ALL or history of cancer (other than basal cell skin cancer or carcinoma of the cervix in situ, or other localised cancer treated by surgical excision only more than 5 years earlier without evidence of recurrence in the intervening period).
6. Positive for HIV, or evidence of uncontrolled Hepatitis B or C infection
7. Severe active infection
8. Women who are pregnant at the time of diagnosis will not be excluded from the trial per se. A management plan will be devised between patient, obstetrician and haematologist.

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)
Efficacy
Statistical methods / analysis
The ALL06 B-lineage cohort is the historical control for this study. The ALL06 protocol is adapted from the paediatric ANZCHOG Study 8 protocol, formulated using BFM 2000. Unlike the Study 8 protocol that incorporated novel HR treatment, ALL06 incorporates HR blocks based on the BFM 2000 protocol. The control cohort will be comprised of approximately 65 patients with B-lineage ALL from a total of approximately 85 patients consisting of both T and B-lineage disease from ALL06. The sample population for ALL06 will be otherwise identical to ALL09 and apart from induction blinatumomab cycles will be treated using an identical chemotherapy backbone. The impact of blinatumomab on Day 79 MRD negativity can then be assessed when compared to the historical ALL06 cohort using a phase II Simon’s two-stage design. As a single arm study, there will be no randomisation required. Patients will be stratified as either Standard, Medium, High, Medium High (PPR) or Very High Risk based on previously defined ALL06 prognostic factors.

The expected increase in the rate of MRD negativity, from 60% to 78%, is based on data from the BLAST study in MRD positive R/R ALL15. Based on this data, and the early incorporation of blinatumomab into an induction treatment cycle for de novo B-lineage ALL we feel that this rate of MRD negativity is highly achievable within the context of the proposed trial. The Simon’s two-stage design incorporates an early interim analysis for futility at 16 patients, with 11 or more out 16 responses (MRD negative) required for the trial to continue.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
17/09/2019
Actual
1/10/2019
Date of last participant enrolment
Anticipated
1/03/2022
Actual
Date of last data collection
Anticipated
1/10/2026
Actual
Sample size
Target
53
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 14388 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 14389 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 14390 0
The Alfred - Melbourne
Recruitment hospital [4] 14391 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [5] 14392 0
The Canberra Hospital - Garran
Recruitment hospital [6] 14393 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [7] 14394 0
Gosford Hospital - Gosford
Recruitment hospital [8] 14395 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [9] 14396 0
Prince of Wales Hospital - Randwick
Recruitment hospital [10] 14397 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [11] 14398 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [12] 14399 0
The Townsville Hospital - Douglas
Recruitment hospital [13] 14400 0
Westmead Hospital - Westmead
Recruitment hospital [14] 14401 0
Wollongong Hospital - Wollongong
Recruitment hospital [15] 18642 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [16] 18643 0
Peter MacCallum Cancer Centre - Melbourne
Recruitment postcode(s) [1] 27397 0
5000 - Adelaide
Recruitment postcode(s) [2] 27398 0
2065 - St Leonards
Recruitment postcode(s) [3] 27399 0
3004 - Melbourne
Recruitment postcode(s) [4] 27400 0
3084 - Heidelberg
Recruitment postcode(s) [5] 27401 0
2605 - Garran
Recruitment postcode(s) [6] 27402 0
6150 - Murdoch
Recruitment postcode(s) [7] 27403 0
2250 - Gosford
Recruitment postcode(s) [8] 27404 0
3168 - Clayton
Recruitment postcode(s) [9] 27405 0
2031 - Randwick
Recruitment postcode(s) [10] 27406 0
4102 - Woolloongabba
Recruitment postcode(s) [11] 27407 0
2050 - Camperdown
Recruitment postcode(s) [12] 27408 0
4814 - Douglas
Recruitment postcode(s) [13] 27409 0
2145 - Westmead
Recruitment postcode(s) [14] 27410 0
2500 - Wollongong
Recruitment postcode(s) [15] 33011 0
3050 - Parkville

Funding & Sponsors
Funding source category [1] 300961 0
Charities/Societies/Foundations
Name [1] 300961 0
CanTeen Australia
Address [1] 300961 0
161 Flemington Road, Melbourne VIC 3000
Country [1] 300961 0
Australia
Funding source category [2] 300962 0
Commercial sector/Industry
Name [2] 300962 0
Amgen
Address [2] 300962 0
115 Cotham Rd, Kew VIC 3101
Country [2] 300962 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Australasian Leukaemia and Lymphoma Group
Address
35 Elizabeth St, Richmond VIC, 3121
Country
Australia
Secondary sponsor category [1] 300535 0
None
Name [1] 300535 0
Address [1] 300535 0
Country [1] 300535 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301726 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 301726 0
Level 3, Roma Mitchell House
North Terrace, Adelaide SA
Australia 5000
Ethics committee country [1] 301726 0
Australia
Date submitted for ethics approval [1] 301726 0
22/10/2018
Approval date [1] 301726 0
21/05/2019
Ethics approval number [1] 301726 0

Summary
Brief summary
The purpose of this study is to determine if a new immune based therapy (called Blinatumomab) can help improve outcomes for patients with Acute Lymphoblastic Leukaemia.

Who is it for?

You may be eligible for this study if you are aged 15-40 and have been diagnosed with B-lineage Acute Lymphoblastic Leukaemia.

Study details

All participants in this study will be provided with Blinatumomab, that will be provided continuously through the vein over two cycles of 28 days using an infusion device. Participants will be provided with usual care outside of these two cycles.
79 days after commencing cycle 1, participants will need to take a blood test and a bone marrow sample will be collected.

Blood and bone marrow samples will also be taken throughout the treatment period, however these are the same as you would have taken during standard treatment outside of the trial.

It is hoped that this study will help to better understand how to successfully incorporate immune based therapy in adolescents and young adults with Acute Lymphoblastic Leukaemia.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87902 0
Dr Matthew Greenwood
Address 87902 0
Department of Haematology, Royal North Shore Hospital
Reserve Rd, St Leonards NSW 2065
Country 87902 0
Australia
Phone 87902 0
+61 2 9926 7118
Fax 87902 0
Email 87902 0
matthew.greenwood@health.nsw.gov.au
Contact person for public queries
Name 87903 0
Dr Matthew Greenwood
Address 87903 0
Department of Haematology, Royal North Shore Hospital
Reserve Rd, St Leonards NSW 2065
Country 87903 0
Australia
Phone 87903 0
+61 2 9926 7118
Fax 87903 0
Email 87903 0
matthew.greenwood@health.nsw.gov.au
Contact person for scientific queries
Name 87904 0
Dr Matthew Greenwood
Address 87904 0
Department of Haematology, Royal North Shore Hospital
Reserve Rd, St Leonards NSW 2065
Country 87904 0
Australia
Phone 87904 0
+61 2 9926 7118
Fax 87904 0
Email 87904 0
matthew.greenwood@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No individual participant data will be publicly available as it is the aggregate data that is under investigation.
What supporting documents are/will be available?
No other documents available
Summary results
No Results