Acute Lymphoblastic Leukemia MedDRA version: 21.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864
Conditions
Interventions
Sponsors
Princess Máxima Center for Pediatric Oncology
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must be treated according to Interfant-06 backbone 2. Patients must have newly diagnosed, CD19 positive, B-precursor acute lymphoblastic leukemia 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 (see table 1), 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 Are the trial subjects under 18? yes Number of subjects for this age range: 30 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 1.5 X ULN, based on the normal ranges for age and gender of the local laboratories 4. Total 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the safety of 1 course of blinatumomab added to the Interfant-06 backbone in infants with newly diagnosed ALL.;Secondary Objective: - to assess the feasibility of adding 1 course of blinatumomab to the Interfant-06 backbone - to define the preliminary response rate of this regimen - to assess pharmacokinetics of blinatumomab in infants;Primary end point(s): 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. ;Timepoint(s) of evaluation of this end point: Continuously through treatment and safety follow-up | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Toxicity/feasibility: 1. Incidence and severity of (serious) adverse events, independently to relationship with blinatumomab 2. Number of treatment interruptions due to toxicity occurring during blinatumomab 3. Proportion of patients that receive a full course (4 weeks) of blinatumomab 4. Incidence and severity of key safety parameters till start of maintenance and during long-term follow-up Activity/Efficacy: 5. MRD response at the following time-points: TP2 d33 (end of induction), TPblina1 d15 (after initial 15 days of blinatumomab) and TPblina2 d29 (after the complete course of blinatumomab) 6. MRD response at the following time-points: TP2 d33 (end of induction) and TP4 (end of Protocol IB) 7. Proportion of MR patients with MRD = 5x10-4 before OCTADAD (indication for SCT) 8. cCR/CR and 6 months post-induction EFS and the long-term EFS and OS Pharmacokinetics: 9. Steady state concentration of blinatumomab (Css) ;Timepoint(s) of evaluation of this end point: Continuously through treatment and safety follow-up | — |
Countries
Australia, Austria, Belgium, Czechia, Czech Republic, Denmark, France, Germany, Italy, Netherlands, United Kingdom
Contacts
Public ContactTrialmanager DCOG-ECTC
Princess Máxima Center for Pediatric Oncology
Outcome results
None listed