Study of Blinatumomab in Japanese Patients With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

A Phase 1b/2 Study of Blinatumomab in Japanese Subjects With Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia (ALL) (Horai Study)

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.

The Phase 1b part will investigate the safety, efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of blinatumomab to determine the maximum tolerated dose (MTD) in both adult and pediatric Japanese patients with relapsed/refractory B-precursor ALL. The Phase 2 part will assess the safety and efficacy of the recommended dose level of blinatumomab identified in the Phase 1b portion of the study in the adult study population.

In June 2017 protocol amendment 4 extended the study to include an expansion cohort of approximately 65 participants to investigate the safety of blinatumomab in participants who did not participate in Phase 1b or Phase 2 of the study. Adult and pediatric patients in the expansion cohort may receive up to 5 cycles of investigational blinatomumab and may receive commercial blinatomumab after a minimum of 2 cycles of the investigational drug.

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