This study is a treatment protocol with blinatumomab for infants under 1 year old who are diagnosed with acute lymphoblastic leukemia with a specific unfavorable genetic alteration. The purpose of the study is to improve the outcome of this disease in infants.
All infants that are eligible for this study and for whom the parents/legal representatives give informed consent will be enrolled in this study. All patients will receive one cycle of blinatumomab on top of the standard treatment backbone after induction therapy. Medium risk patients, that respond well to the 1st cycle will be treated with a 2nd cycle of blinatumomab replacing one chemo course after consolidation therapy. If they do not respond well enough they will be treated according to the current treatment standard. Minimal residual disease will be used to determine the response to blinatumomab. High risk patients will be eligible for allogeneic stem cell transplantation after the first blinatumomab cycle if they are Minimal Residual Disease (MRD) negative (defined as \< 0.01%). Also medium risk patients with insufficient MRD response after induction or after the 1st cycle of blinatumomab will be allocated to high risk treatment and will be eligible for allogeneic stem cell transplantation.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
160
1st cycle: 15 μg/m2/day as a 4 week continuous IV infusion for patients with a M1 marrow. For patients with a M2/M3 marrow a step-dosing strategy is required with a dose of 5 μg/m2/day in week 1 followed by 15 μg/m2/day in weeks 2, 3, and 4.
2nd cycle: 15 μg/m2/day as a 4 week continuous iv infusion
Event free survival (EFS).
The primary endpoint is EFS, defined as the time from diagnosis to resistance to induction, relapse, death from any cause or second malignancy (whichever occurs first), or time to last follow-up (censored) for patients without events.
Time frame: 5 years
Overall survival
The endpoints for analysis by risk group will be EFS, cumulative incidence (or percentage) of resistance to induction, cumulative incidence of relapse (CIR), death in complete remission (CR) and second malignancy.
Time frame: 8 years
Endpoints by risk group
The endpoints for analysis by risk group will be EFS, cumulative incidence (or percentage) of resistance to induction, cumulative incidence of relapse (CIR), death in complete remission (CR) and second malignancy.
Time frame: 8 years
Outcome for the entire study cohort and according to risk group
Outcome for the entire study cohort and according to risk group will be evaluated in terms of the protocol specific definition of EFS follows: the time from diagnosis to, resistance to proto-col, relapse, death from any cause or second malignancy (whichever occurs first), or time to last follow-up for patients without events. Cumulative incidence (or percentage) of resistance, CIR, death in CR and second malignancy will also be estimated.
Time frame: 8 years
Minimal Residual Disease
MRD response as defined in the protocol and frequencies of MRD levels
Time frame: 8 years
CD19 (cluster of differentiation antigen 19) negative relapse
Proportion of CD19 negative relapses in the entire study cohort and according to risk group
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Hospital de Pediatría S.A.M.I.C. "Juan P. Garrahan"
Buenos Aires, Argentina
RECRUITINGAustralian and New Zealand Children's Haematology/Oncology Group
Clayton, Victoria, Australia
ACTIVE_NOT_RECRUITINGNorth Adelaide- Womens and Childrens Hospital
Adelaide, Australia
ACTIVE_NOT_RECRUITINGMonash Children's Hosptial
Clayton, Australia
ACTIVE_NOT_RECRUITINGNew Lambton Heights- John Hunter Children's Hospital
New Lambton Heights, Australia
ACTIVE_NOT_RECRUITINGRoyal Children's Hospital (Children's Cancer Centre)
Parkville, Australia
ACTIVE_NOT_RECRUITINGPerth Children's Hospital
Perth, Australia
ACTIVE_NOT_RECRUITINGQueensland Children's Hospital
South Brisbane, Australia
ACTIVE_NOT_RECRUITINGSydney Childrens Hospital
Sydney, Australia
ACTIVE_NOT_RECRUITINGThe Childrens Hospital at Westmead
Westmead, Australia
ACTIVE_NOT_RECRUITING...and 102 more locations
Time frame: 8 years
Myeloid lineage switches
Proportion of myeloid lineage switches in the entire study cohort and according to risk group
Time frame: 8 years
Grade ≥3 adverse event
Proportion of grade ≥3 adverse event (AEs) during the blinatumomab course(s). Proportion of adverse events of special interest (AESIs) and serious adverse events (SAEs) in all protocol phases.
Time frame: 8 years
Grade ≥2 cardiac disorders
Proportion of grade ≥2 cardiac disorders at 2 and 5 years after diagnosis
Time frame: 5 years
Overall survival after 1st relapse
Overall survival (OS) after first relapse, defined as the time from first relapse to death from any cause, in the entire study cohort and according to risk group
Time frame: 8 years