Phase 2
N=66
Study of Blinatumomab in Japanese Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia
Relapsed Refractory B Precursor Acute Lymphoblastic Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT02412306 ↗Enrolled (actual)
66
Serious AEs
19.7%
Results posted
Jan 2020
Primary outcome: Primary: Phase 1b: Number of Participants With Dose-limiting Toxicities — 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Blinatumomab (Drug)
- Age
- Pediatric, Adult, Older Adult · 0+ yrs
- Sex
- All
- Sponsor
- Amgen
- Primary completion
- Feb 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1b: Number of Participants With Dose-limiting Toxicities |
0; 0 | — |
| PRIMARY Phase 2: Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment |
38.1 | — |
| PRIMARY Expansion Cohort: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs |
14; 17; 11; 15; 7; 7 | — |
| SECONDARY Phase 1b Adults: Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment |
80.0 | — |
| SECONDARY Phase 1b Pediatric: Percentage of Participants With M1 Remission Within 2 Cycles of Treatment |
55.6 | — |
| SECONDARY Phase 1b and Phase 2: Duration of Response |
13.0; 2.3; 13.1 | — |
| SECONDARY Phase 1b and Phase 2: Relapse-free Survival |
11.4; 2.3; 13.1 | — |
| SECONDARY Phase 1b and Phase 2: Overall Survival |
11.0; 10.6; 14.8 | — |
| SECONDARY Phase 2: Best Overall Response Within 2 Cycles of Treatment |
5; 3; 0; 6; 0; 0 | — |
| SECONDARY Phase 2: Percentage of Participants Who Received an Allogeneic Hematopoietic Stem Cell Transplant (HSCT) During Blinatumomab Induced Remission |
81.0 | — |
| SECONDARY Phase 2: 100-Day Mortality After Allogeneic HSCT |
11.8 | — |
| SECONDARY Phase 1b and Phase 2: Number of Participants With TEAEs |
5; 9; 21; 4; 9; 21 | — |
| SECONDARY Phase 1b and Phase 2: Serum Blinatumomab Concentration at Steady State |
191; 113; 135; 107; 948; 361 | — |
| SECONDARY Phase 1b and Phase 2: Systemic Clearance of Blinatumomab |
1.59; 1.88; 1.59; 1.83 | — |
| SECONDARY Phase 1b and Phase 2: Terminal Half-life of Blinatumomab |
2.38; 1.92; 2.60; 2.62 | — |
| SECONDARY Phase 1b and Phase 2: Volume of Distribution of Blinatumomab |
6.02; 5.05; 8.22; 6.38 | — |
| SECONDARY Phase 1b and Phase 2: Number of Participants Who Developed Anti-Blinatumomab Antibodies |
0; 0; 0 | — |
| SECONDARY Phase 1b and Phase 2: Interleukin-2 Concentration |
16.1; 30.2; 10.0; 32.6; 10.0; 17.2 | — |
| SECONDARY Phase 1b and Phase 2: Interleukin-6 Concentration |
29.1; 173; 275; 186; 317; 246 | — |
| SECONDARY Phase 1b and Phase 2: Interleukin-10 Concentration |
101; 597; 153; 423; 230; 400 | — |
| SECONDARY Phase 1b and Phase 2: Tumor Necrosis Factor-Alpha (TNFα) Concentration |
37.3; 24.1; 15.8; 20.1; 15.8; 10.0 | — |
| SECONDARY Phase 1b and Phase 2: Interferon Gamma (IFN-γ) Concentration |
26.2; 52.3; 41.2; 65.8; 64.5; 42.1 | — |
| SECONDARY Expansion Cohort Adult: Percentage of Participants With a Best Response of Complete Remission or Complete Remission With Only Partial Hematological Recovery Within 2 Cycles of Treatment |
78.6 | — |
| SECONDARY Expansion Cohort Pediatric: Percentage of Participants With M1 Remission Within 2 Cycles of Treatment |
29.4 | — |
Summary
This is an open-label, combined 2-part multicenter study to evaluate the efficacy, safety, and tolerability of blinatumomab in adult and pediatric Japanese patients with relapsed/refractory B-precursor ALL.
Eligibility Criteria
Adult Subjects Key Inclusion Criteria:
- Age ≥ 18 years old at enrollment
- Subjects with Philadelphia-negative B-precursor ALL, with any of the following:
- Relapsed or refractory after first line therapy with first remission duration ≤ 12 months; or
- Relapsed or refractory after first salvage therapy; or
- Relapsed or refractory within 12 months of allogeneic hematopoietic stem cell transplant (alloHSCT)
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
- Greater than 5% blasts in bone marrow
Pediatric Subjects Key Inclusion Criteria:
- Age < 18 years old at enrollment
- Relapsed/refractory disease, defined as one of the following:
- second or later bone marrow relapse;
- any marrow relapse after alloHSCT; or
- Refractory to other treatments:
- For subjects in first relapse: failure to achieve a complete response (CR) following a full standard reinduction chemotherapy regimen
- For subjects who have not achieved a first remission: failure to achieve remission following a full standard induction regimen
- Greater than 5% blasts in bone marrow
- Karnofsky performance status ≥ 50% for subjects ≥ 16 years
- Lansky performance status ≥ 50% for subjects < 16 years
Key Exclusion Criteria
- Subjects with Burkitt´s Leukemia according to World Health Organization (WHO) classification
- History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis; with the exception of well-controlled CNS leukemia
- Active ALL in the CNS or testes
- Current autoimmune disease or history of autoimmune disease with potential CNS involvement
- Autologous HSCT within 6 weeks prior to start of blinatumomab treatment
- AlloHSCT within 12 weeks prior to start of blinatumomab treatment
- Any active acute Graft-versus-Host Disease (GvHD) grade 2-4 according to Glucksberg criteria or active chronic GvHD requiring systemic treatment
Data sourced from ClinicalTrials.gov (NCT02412306). 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.