Acute Lymphoblastic Leukemia, Mixed Phenotype Acute Leukemia
Conditions
Keywords
infant under one year, KMT2A-wildtype
Brief summary
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.
Detailed description
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.
Interventions
DRUGBlinatumomab
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.
Sponsors
Princess Maxima Center for Pediatric Oncology
University of Milano Bicocca
Amgen Europe B.V
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Definition: Provide details about the Interventional Study Model. Limit: 1000 characters.
Eligibility
Sex/Gender
ALL
Age
1 Days to 1 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with newly diagnosed B- precursor ALL or B-cell MPAL (single lineage) according to the WHO classification of tumours of haematopoietic and lymphoid tissues (revised 4th edition 2017), with KMT2A-rearrangement. 2. ≤ 365 days of age at the time of diagnosis of ALL. 3. Written informed consent of the parent(s) or other legally authorized guardian of the patient according to local law and regulations.
Exclusion criteria
for blinatumomab: 1. KMT2A-wildtype patients. 2. Multilineage MPAL 3. T-ALL. 4. Age \> 365 days at the time of diagnosis. 5. Down syndrome. 6. Relapsed ALL. 7. Treatment with systemic corticosteroids (equivalent prednisone \>10 mg/m2/day) for more than one week and/or any chemotherapeutic agent in the 4-week interval prior to diagnosis. Patients who received corticosteroids by aerosol are eligible for the study. If
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event free survival (EFS). | 5 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | 8 years | 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. |
| Endpoints by risk group | 8 years | 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. |
| Outcome for the entire study cohort and according to risk group | 8 years | 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. |
| Minimal Residual Disease | 8 years | MRD response as defined in the protocol and frequencies of MRD levels |
| CD19 (cluster of differentiation antigen 19) negative relapse | 8 years | Proportion of CD19 negative relapses in the entire study cohort and according to risk group |
| Myeloid lineage switches | 8 years | Proportion of myeloid lineage switches in the entire study cohort and according to risk group |
| Grade ≥3 adverse event | 8 years | 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. |
| Grade ≥2 cardiac disorders | 5 years | Proportion of grade ≥2 cardiac disorders at 2 and 5 years after diagnosis |
| Overall survival after 1st relapse | 8 years | 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 |
Countries
Argentina, Australia, Austria, Belgium, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Lithuania, Netherlands, New Zealand, Norway, Portugal, Saudi Arabia, Slovakia, Spain, Sweden
Contacts
CONTACTLieke van den Wildenberg
CONTACTPeggy Scholte-Van Houtem
PRINCIPAL_INVESTIGATORJanine Stutterheim, Dr
Princess Maxima Center for Pediatric Oncology in The Netherlands
Outcome results
None listed