Primary Objective:To estimate the incidence of treatment-emergent and treatment-related adverse eventsduring treatment with blinatumomab in pediatric and adolescent subjects with B-precursorALL in second or later bone marrow relapse, in any marrow relapse after alloHSCT, orrefractory to other treatmentsSecondary Objective(s):To describe key efficacy outcomes, including incidence of complete response (CR) within 2cycles of blinatumomab, minimal residual disease (MRD) remission within 2 cycles ofblinatumomab, relapse free survival (RFS), overall survival (OS), incidence of alloHSCT,and 100-day mortality after alloHSCT.Hypotheses:A formal statistical hypothesis will not be tested. The incidence of treatment-emergentand treatment-related adverse events will be estimated.Study Endpoints: - Incidence of treatment-emergent and treatment-related adverse events - Incidence of CR within 2 cycles of blinatumomab - MRD remission within 2 cycles of blinatumomab - RFS - OS - Incidence of alloHSCT - 100-day mortality after alloHSCTStudy Design:Multi-center, open-label, single-arm expanded access protocol
Not Provided
Drug: Blinatumomab
A single cycle of blinatumomab (CIVI) treatment is 6wks, 4wks of treatment followed by a
2wk treatment-free interval. Up to 5 cycles will be administered per subject. In the
first cycle, for patients with an M3 bone marrow, the initial dose will be 5μg/m2/day for
the first 7days, escalated to 15μg/m2/day on D8-D29. For all subsequent cycles
15μg/m2/day will be the dose for all 4wks of continuous treatment. In case of M2 bone
marrow or M1 bone marrow with an MRD relapse at screening, the initial dose will start at
15μg/m2/day for the first 7days of treatment & no dose step at D8. For all subsequent
cycles the dose will remain 15μg/m2/day. A dose of 9μg/day for the initial dose (if
applicable) & 28μg/day for the escalated dose after dose step should not be exceeded.
Other Name: AMG103, Blincyto
Other: Extension of LTFU as per ProtocolAmendment7 7Jun18
LTFU (Long Term Follow-Up) will extend past 18 months for patients already ended the
study/still on study or to be enrolled at European sites if they did not receive a
transplantation after blinatumomab treatment. For subjects to be included in the
additional LTFU, data will be captured until subjects are 18yrs old (every 6 months by
phone contact). The following will be captured: relapse (medullary or extra-medullary
relapse and its specific location), second tumor (which type), alive/died and cause of
death, hospitalization and reason for hospitalization.
Inclusion Criteria 101 Immunophenotypic evidence of CD19 positive B-precursor ALL (pro
B-, pre B-, common ALL) 102 Age > 28 days and < 18 years at the time of informed
consent/assent 103 Morphological or molecular evidence of relapsed/refractory disease,
defined as one of the following:
- Second or later bone marrow relapse (defined as M3 marrow or M2 marrow or M1 marrow
but with MRD level ≥ 10E-3), or
- Any marrow relapse after alloHSCT (defined as M3 marrow or M2 marrow or M1 marrow
but with and MRD level ≥ 10E-3), or
- Refractory to other treatments:
- For patients in first relapse: failure to achieve a CR following a full
standard reinduction chemotherapy regimen
- For patients who have not achieved a first remission: failure to achieve
remission following a full standard induction regimen
- Subjects previously treated with blinatumomab may be eligible, if subject ended
treatment for reason(s) other than disease progression or intolerability to
blinatumomab (Note: This does not include patients who have already received
blinatumomab treatment on this study, but refers only to patients outside of the
20130320 study)
Other Inclusion Criteria may apply
Exclusion Criteria 201 Any active acute Graft-versus-Host Disease (GvHD) grade 2 to grade
4 according to the Glucksberg criteria or active chronic GvHD requiring systemic
treatment 202 Immunosuppresive agents to prevent or treat GvHD within 2 weeks prior to
blinatumomab treatment (except for topical corticosteroids) 203 Active (overt) ALL in the
CNS (confirmed by cerebrospinal fluid [CSF] analysis) or in testes
Other Exclusion Criteria may apply
Research Site
Aurora, Colorado, United States
Research Site
Cincinnati, Ohio, United States
Research Site
Memphis, Tennessee, United States
Research Site
Salt Lake City, Utah, United States
Research Site
Wien, Austria
Research Site
Marseille cedex 5, France
Research Site
Paris, France
Research Site
Berlin, Germany
Research Site
Frankfurt am Main, Germany
Research Site
Kiel, Germany
Research Site
München, Germany
Research Site
Münster, Germany
Research Site
Tübingen, Germany
Research Site
Würzburg, Germany
Research Site
Monza (MB), Italy
Research Site
Padova, Italy
Research Site
Roma, Italy
Research Site
Zuerich, Switzerland
Research Site
Sheffield, United Kingdom
MD, Study Director
Amgen