acute lymphoblastic leukemia (ALL) Acute lymfatische leukemie (ALL)
Conditions
Interventions
Blinatumomab is added to the standard arm of the Interfant-06 backbone (IA-IB-MARMA-OCTADAD-maintenance). After induction therapy (IA) patients will receive 1 course of blinatumomab 15 ìg/m2/day as a
Sponsors
Princess Maxima Center for Pediatric Oncology
Eligibility
Inclusion criteria
Inclusion criteria: In order to be eligible to participate in this study, a patient must meet all of the following 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. 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
Exclusion criteria
Exclusion criteria: A potential patient who meets any of the following criteria will be excluded from participation in this study: 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) 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 |
|---|---|
| Primary endpoint 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints 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) | — |
Contacts
Public ContactI.M. van der Sluis
Princess Maxima Center for Pediatric Oncology, Heidelberglaan 25, 3584 CS Utrecht
Outcome results
None listed