Phase 3
N=111
Phase 3 Trial of Blinatumomab vs Standard Chemotherapy in Pediatric Subjects With HIgh-Risk (HR) First Relapse B-precursor Acute Lymphoblastic Leukemia (ALL)
Leukemia, Acute Lymphoblastic
Bottom Line
View on ClinicalTrials.gov: NCT02393859 ↗Enrolled (actual)
111
Serious AEs
36.8%
Results posted
Jul 2020
Primary outcome: Primary: Kaplan Meier Estimate: Event-Free Survival (EFS; Primary Analysis) — 7.4; NA months — p=< 0.001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Blinatumomab (Drug); Dexamethasone (Drug); Vincrisitne (Drug); Daunorubicin (Drug); Methotrexate (Drug); Ifosfamide (Drug); PEG-asparaginase (Drug); Erwinia-asparaginase (Drug)
- Age
- Pediatric · 0+ yrs
- Sex
- All
- Sponsor
- Amgen
- Primary completion
- Jul 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Kaplan Meier Estimate: Event-Free Survival (EFS; Primary Analysis) |
7.4; NA | < 0.001 sig |
| PRIMARY Kaplan Meier Estimate: EFS (Final Analysis) |
7.8; NA | < 0.001 sig |
| SECONDARY Kaplan Meier Estimate: Overall Survival (OS) |
25.6; NA | 0.001 sig |
| SECONDARY Percentage of Participants With an MRD Response Within 29 Days of Treatment Initiation |
53.1; 93.9; 60.0; 92.6 | < 0.001 sig |
| SECONDARY Cumulative Incidence of Relapse (CIR) |
7.9; NA | — |
| SECONDARY Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events (TRAEs) |
50; 54; 43; 33; 24; 15 | — |
| SECONDARY Number of Participants With TEAEs of Interest |
1; 0; 1; 0; 1; 0 | — |
| SECONDARY Number of Participants With Shifts From Baseline Grade 0 or 1 to Worst Postbaseline Grade 3 or 4 Clinical Chemistry and Hematology Values |
0; 1; 4; 5; 1; 1 | — |
| SECONDARY Kaplan-Meier Estimate of 100-Day Mortality After Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) |
5.1; 3.9 | — |
| SECONDARY Number of Participants With Anti-Blinatumomab Antibodies Postbaseline (Blinatumomab Arm Only) |
0; 0 | — |
| SECONDARY Pharmacokinetics: Concentration at Steady State (Css) (Blinatumomab Arm Only) |
884 | — |
| SECONDARY Pharmacokinetics: Clearance (CL) (Blinatumomab Arm Only) |
1.14 | — |
Summary
B-precursor ALL is an aggressive malignant disease. Therapy is usually stratified according to risk characteristics to ensure that appropriate treatment is administered to patients with high-risk of relapse. In general, pediatric treatment regimens are more intense than those employed in adults and include courses of combination chemotherapy. Standard of care chemotherapy is associated with considerable toxicity. There is a lack of novel treatment options for subjects who relapse or are refractory to treatment. Therefore, innovative therapeutic approaches are urgently needed. Blinatumomab is a bispecific single-chain antibody construct designed to link B cells and T cells resulting in T cell activation and a cytotoxic T cell response against CD19 expressing cells. This study will evaluate the event-free survival (EFS) after treatment with blinatumomab when compared to standard of care (SOC) chemotherapy. The effect of blinatumomab on overall survival and reduction of minimal residual disease compared to SOC chemotherapy will also be investigated.
Eligibility Criteria
Inclusion Criteria
- Subjects with Philadelphia chromosome negative (Ph-) high-risk (HR) first relapse B-precursor acute lymphoblastic leukemia (ALL; as defined by International Berlin-Frankfurt-Muenster study group/International study for treatment of childhood relapsed ALL [I-BFM SG/IntReALL] criteria)
- Subjects with bone marrow blast percentage 28 days and 3.0 mg/dL prior to start of treatment (unless related to Gilbert's or Meulengracht disease)
- Documented infection with human immunodeficiency virus (HIV)
- Known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing (excluding asparaginase)
- Post-menarchal female subject who is pregnant or breastfeeding, or is planning to become pregnant or breastfeed while receiving protocol-specified therapy and for at least 12 months after the last dose of chemotherapy
- Post-menarchal female subject who is not willing to practice true sexual abstinence or use a highly effective form of contraception while receiving protocol-specified therapy and for at least 12 months after the last dose of chemotherapy
- Sexually mature male subject who is not willing to practice true sexual abstinence or use a condom with spermicide while receiving protocol-specified therapy and for at least 6 months after last dose of chemotherapy. In countries where spermicide is not available, a condom without spermicide is acceptable
- Sexually mature male subject who is not willing to abstain from sperm donation while receiving protocol-specified therapy and for at least 6 months after last dose of chemotherapy
- Subject likely to not be available to complete all protocol-required study visits or procedures, including follow-up visits, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge
- History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion
- Placed into an institution due to juridical or regulatory ruling.
Data sourced from ClinicalTrials.gov (NCT02393859). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.