A Study of Subcutaneous Blinatumomab in Children With R/R and and MRD+ B-Cell Precursor Acute Lymphoblastic Leukemia

A Phase 1b/2 Study to Investigate the Safety, Efficacy and Pharmacokinetics of Administration of Subcutaneous (SC) Blinatumomab in Pediatric Participants With Relapsed/Refractory (R/R) and Minimal Residual Disease Positive (MRD+) B-Cell Precursor Acute Lymphoblastic Leukemia (B-ALL)

The main objective of this study is to evaluate the safety and efficacy of SC blinatumomab in children below 12 years of age.

Inclusion Criteria:

• Age ≥28 days to <12 years at the time of informed consent/assent.

• Lansky Performance Status (LPS) of ≥ 50%.

• For Phase 1b and Phase 2 cohort in participants with R/R B-ALL:

  • Participants with B-ALL relapsed after or refractory to any line of treatment including allogeneic hematopoietic stem cell transplant (HSCT).
  • Greater than or equal to 5% blasts in the bone marrow (BM) is considered as relapse in the BM.

• For Phase 2 cohort in participants with MRD+ B-ALL:

  • Participants with MRD+ B-ALL must have between ≥ 0.1% and < 5% blasts in the BM.

• Prior CD19-directed therapy will be allowed (with demonstrated continued CD19+ expression) if treatment ended >4 weeks prior to start of protocol therapy and no prior central nervous system (CNS) complications.

• Any Philadelphia chromosome-positive (Ph+) participant intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.

Exclusion Criteria:

• Active ALL in the CNS.
• History or presence of clinically relevant CNS pathology or event such as epilepsy, childhood seizure, paresis, aphasia, stroke, severe brain injuries, cerebellar disease, organic brain syndrome, psychosis, or severe (≥ grade 3) CNS events including immune effector cell-associated neurologic syndrome (ICANS) from prior CAR-T or other T-cell engager therapies.
• Isolated EM disease.
• Current autoimmune disease or history of autoimmune disease with potential CNS involvement.
• Patients with Down Syndrome are not eligible for this study.
• Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication.
• Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus.
• Presence of an acute or uncontrolled chronic infection, or any other concurrent disease or medical condition that could be worsened by the treatment or interfere with the participant's ability to comply with the study protocol.
• Allogeneic HSCT within 12 weeks before the start of blinatumomab.