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Trial registered on ANZCTR


Registration number
ACTRN12620000542998
Ethics application status
Approved
Date submitted
19/03/2020
Date registered
4/05/2020
Date last updated
4/05/2020
Date data sharing statement initially provided
4/05/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
Blinatumomab in infant acute lymphoblastic leukemia (ALL)
Scientific title
A pilot study to test the feasibility, safety and efficacy of the addition of the BiTE antibody Blinatumomab to the Interfant-06 backbone in infants with MLL-rearranged acute lymphoblastic leukemia. A collaborative study of the Interfant network.
Secondary ID [1] 300824 0
NTR6359
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukemia 316709 0
Condition category
Condition code
Cancer 314957 314957 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The patient will have been treated according to the Interfant-06 protocol where they will have received standard induction therapy. If the patient is eligible for the current study, blinatumomab will be added to standard arm (1B) of the Interfant-06 protocol. The patient will receive 1 course of blinatumomab. The blinatumomab course (15 micrograms/m2/day) consists of a 4-week continuous intravenous infusion. The patient will be closely monitored during the first 72 hours of treatment and will be admitted to the hospital preferably for the full 4 weeks of the blinatumomab infusion with a minimum admission of 7 days. Following treatment with blinatumomab, the patient wil lrecommence standard treatment according to Interfant-06 (protocol 1B).
Intervention code [1] 317153 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323264 0
Incidence of clinically relevant toxicities defined as any toxicity that is possibly or definitely attributable to blinatumomab AND results in permanent discontinuation of blinatumomab OR death. Adverse events will be reported spontaneously by the subject or as observed by the investigator or their staff.
Timepoint [1] 323264 0
Assessed continuously throughout the 4 week treatment period, Safety follow up at ~11 weeks from day 1 of treatment.
Secondary outcome [1] 381352 0
Incidence and severity of (serious) adverse events, assessed according to the Criteria for Adverse Events (CTCAE) v4.03, independently to relationship with blinatumomab.

Timepoint [1] 381352 0
Incidence and severity of serious adverse events assessed continuously throughout the 4 week treatment period, in safety follow up, 7 weeks post treatment completion, and long term follow up, 2.5 years after the last patient in, every 6 months.
Secondary outcome [2] 381769 0
Number of treatment interruptions due to toxicity occurring during blinatumomab.
Timepoint [2] 381769 0
Number of treatment interruptions due to toxicity assessed at the end of the 4-week treatment period.
Secondary outcome [3] 381770 0
Proportion of patients that receive a full course (4 weeks) of blinatumomab
Timepoint [3] 381770 0
The proportion of patients that receive a full course of blinatumomab will be calculated once the study has been closed to accrual.
Secondary outcome [4] 381771 0
Incidence and severity of key safety parameters, assessed according to the Criteria for Adverse Events (CTCAE) v4.03, in terms of incidence and rates
Timepoint [4] 381771 0
Incidence and severity of serious adverse events assessed continuously throughout the 4 week treatment period, in safety follow up, 7 weeks post treatment completion, and long term follow up, 2.5 years after the last patient in, every 6 months.
Secondary outcome [5] 381772 0
MRD response measured as the MRD level assessed using polymerase chain reaction (PCR).
Timepoint [5] 381772 0
MRD response will be assessed at the following timpoints: TP2 d33 (end of induction), TPblina1 d15 (after initial 15 days of blinatumomab) and TPblina2 d29 (after the complete course of blinatumomab)
Secondary outcome [6] 381773 0
MRD response measured as the MRD level assessed using PCR.
Timepoint [6] 381773 0
MRD response at the following time-points: TP2 d33 (end of induction) and TP4 (end of Protocol IB)
Secondary outcome [7] 381774 0
Proportion of medium risk patients with MRD > 5x10-4, assessed using PCR, before OCTADAD (indication for SCT) will be calculated.
Timepoint [7] 381774 0
The proportion of MR patients with MRD> 5x10-4 before OCTADAD will be calculated once the study has been closed to accrual.
Secondary outcome [8] 381775 0
Event Free Survival (EFS) measured as time from study entry to disease progression, relapse, death from any cause or second malignancy and will be assessed using documentation of disease/survival status that includes cCR, CR, MRD, relapse, death/cause of death.


Timepoint [8] 381775 0
EFS will be estimated at 6 months post induction. Disease/survival status documented at Day 15 of treatment, end of treatment, safety follow up, 7 weeks post treatment, and long-term follow up, 2.5 years after the last patient in, every 6 months.
Secondary outcome [9] 381776 0
Steady state concentration of blinatumomab (Css) assessed using a serum assay.
Timepoint [9] 381776 0
Steady state concentration assessed continuously throughout the 4 week treatment period,
Secondary outcome [10] 382261 0
Overall Survival (OS) measured as the time from study entry to death from any cause. Documentation of disease/survival will include cCR, CR, MRD, relapse, death/cause of death and will be assessed using documentation of disease/survival status that includes cCR, CR, MRD, relapse, death/cause of death.
Timepoint [10] 382261 0
OS will be estimated at 6 months post-induction and in long-term follow-up, 2.5 years after the last patient in, every 6 months. Disease/survival status documented at Day 15 of treatment, end of treatment, safety follow up, 7 weeks post treatment, and long-term follow up, 2.5 years after the last patient in, every 6 months.

Eligibility
Key inclusion criteria
1. Patients must be treated according to Interfant-06 backbone
2. Patients must have newly diagnosed, CD19 positive, B-precursor ALL
3. Morphological verification of the diagnosis, confirmed with immunophenotyping
4. < 365 days of age at time of diagnosis of ALL
5. > 28 days of age at start of blinatumomab administration
6. MR and HR patients according to risk stratification of the Interfant-06 protocol, thus including all MLL-rearranged and MLL not-evaluable patients (these latter are stratified and treated according to MR).
7. M1 or M2 bone marrow after induction (~day 33).
If the peripheral blood shows pancytopenia at day 33 it is justified to postpone the bone marrow puncture according to the Interfant-06 protocol. If the bone marrow at day 33 is hypocellular and one is therefore unable to determine M1 or M2 status, then the bone marrow puncture should be repeated.
8. Written informed consent from parents or guardians
Minimum age
28 Days
Maximum age
12 Months
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Biphenotypic ALL
2. Mature B-ALL
3. Presence of t(9;22) (q34;q11) or BCR-ABL fusion transcript
4. M3 marrow after induction
5. Patients with Down syndrome (because of increased toxicity of conventional chemotherapy)
6. Clinically relevant CNS pathology requiring treatment (eg unstable epilepsy)
7. Evidence of CNS involvement of ALL (CNS2 or CNS3) at the end of induction. Subjects with CNS disease at the time of diagnosis are eligible if a CNS1 status is obtained prior to enrolment (lumbar puncture at ~day 29 of induction, see definitions CNS status in Appendix D)
8. Known infection with human immunodeficiency virus (HIV)
9. Known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing

Exclusion criteria before start (-d3) of blinatumomab:
1. Peripheral neutrophils <0.5 x 109/l (for M1 marrow only, with a maximum delay of 2 weeks. Patients with M2 bone marrow will not recover their blood counts and can start as soon as the other inclusion criteria are met)
2. Peripheral platelets < 50 x 109/L (for M1 marrow only with a maximum delay of 2 weeks. Patients with M2 bone marrow will not recover their blood counts and can start as soon as the other inclusion criteria are met)
3. Creatinine > 1.5 X ULN, based on the normal ranges for age and gender of the local laboratories
4. Direct bilirubin > 3 x ULN unless the patient has documented Gilbert Syndrome
5. Chemotherapy related toxicities that have not resolved to < grade 2
6. Symptoms and/or clinical signs and/or radiological and/or sonographic signs that indicate an acute or uncontrolled chronic infection, any other concurrent disease or medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol

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
Prospective, international multi-centre study
Phase
Phase 0
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

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,QLD,VIC
Recruitment hospital [1] 16144 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [2] 16145 0
Queensland Children's Hospital - South Brisbane
Recruitment hospital [3] 16146 0
The Royal Childrens Hospital - Parkville
Recruitment postcode(s) [1] 29673 0
2145 - Westmead
Recruitment postcode(s) [2] 29674 0
4101 - South Brisbane
Recruitment postcode(s) [3] 29675 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 305282 0
Government body
Name [1] 305282 0
MRFF, Australian Department of Health
Address [1] 305282 0
Department of Health
GPO Box 9848
Canberra ACT 2601
Australia
Country [1] 305282 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Princess Máxima Center for Pediatric Oncology
Address
Heidelberglaan 25, 3584 CS Utrecht, Netherlands
Country
Netherlands
Secondary sponsor category [1] 305642 0
Other Collaborative groups
Name [1] 305642 0
Australian & New Zealand Childrens Haematology/Oncology Group
Address [1] 305642 0
27-31 Wright Street, Clayton, VIC 3168
Country [1] 305642 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305622 0
Government of Western Australia Child and Adolescent Health Service
Ethics committee address [1] 305622 0
189 Royal Street
East Perth WA 6004
Australia
Ethics committee country [1] 305622 0
Australia
Date submitted for ethics approval [1] 305622 0
Approval date [1] 305622 0
20/02/2018
Ethics approval number [1] 305622 0

Summary
Brief summary
The purpose of this study is to assess the safety of one course of a chemotherapy drug named blinatumomab when added to the Interfant-06 backbone in infants with newly diagnosed acute lymphoblastic leukaemia.

Who is it for?
Your infant may be eligible if they are less than 12 months of age and have been dignosed with acute lymphoblastic leukemia.

Study details
All participants in this study will receive the chemotherapy drug blinatumomab every day for 4 weeks via a needle in the arm.

Some of the tests required for this study are routinely performed as part of standard treatment in children with Infant ALL, such as the bone marrow aspirates, lumbar punctures and most blood tests. Some additional tests and procedures are required.

It is hoped that this research will help determine if blinatumomab is safe for use in infants newly diagnosed with acute lymphoblastic leukemia.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100986 0
Dr Rishi Kotecha
Address 100986 0
Perth Children's Hospital, 15 Hospital Ave, Nedlands WA 6009
Country 100986 0
Australia
Phone 100986 0
+618 6456 4431
Fax 100986 0
Email 100986 0
Rishi.Kotecha@health.wa.gov.au
Contact person for public queries
Name 100987 0
Mrs Robyn Strong
Address 100987 0
Australian & New Zealand Children's Haematology/Oncology Group,
27-31 Wright Street, Clayton VIC 3168
Country 100987 0
Australia
Phone 100987 0
+613 8572 2684
Fax 100987 0
+613 9902 4810
Email 100987 0
Robyn.Strong@hudson.org.au
Contact person for scientific queries
Name 100988 0
Dr Rishi Kotecha
Address 100988 0
Perth Children's Hospital, 15 Hospital Ave, Nedlands WA 6009
Country 100988 0
Australia
Phone 100988 0
+618 6456 4431
Fax 100988 0
Email 100988 0
Rishi.Kotecha@health.wa.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

Only published results and a final summary of results will be available.

At the completion of the study the results will be published in a peer reviewed journal. A summary of the study results will be available on the ANZ Clinical Trials Registry website.
What supporting documents are/will be available?
No other documents available
Summary results
No Results