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Subcutaneous blinatumomab for relapsed/refractory and MRD-positive B-cell precursor ALL

A Phase 1/2 Open-label Study to Investigate the Safety, Efficacy, and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Adults and Adolescents With Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL) and Minimal Residual Disease Positive (MRD+) B-ALL

Phase1; Phase2 Interventional Amgen · NCT04521231

This trial will test whether under-the-skin (subcutaneous) injections of blinatumomab are safe and effective for people aged 12 and older with relapsed/refractory or MRD-positive B-cell precursor acute lymphoblastic leukemia.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment281 (estimated)
Ages12 Years and up
SexAll
SponsorAmgen Industry-sponsored
Drugs / interventionsblinatumomab, CAR T, chimeric antigen receptor, chemotherapy, Immunotherapy
Locations109 sites (Clovis, California and 108 other locations)
Trial IDNCT04521231 on ClinicalTrials.gov

What this trial studies

This is a Phase 1/2, open-label, dose-escalation and dose-expansion program testing subcutaneous formulations of blinatumomab. Phase 1 will find the maximum tolerated dose and a recommended Phase 2 dose using escalating SC doses, while Phase 2 will further test safety, tolerability, efficacy and compare pharmacokinetics of two SC formulations (SC1 and SC2). Eligible participants include adolescents and adults with relapsed/refractory disease (generally ≥5% bone marrow blasts) or MRD-positive disease (0.01%–<5% blasts) according to cohort definitions. The trial is sponsored by Amgen with sites in California and Illinois.

Who should consider this trial

Good fit: People aged 12 years and older with B-cell precursor ALL who are relapsed/refractory or MRD-positive and who meet the trial's bone marrow blast and prior-treatment criteria are the intended candidates.

Not a fit: Patients who do not meet the trial's minimal bone marrow blast thresholds, who have contraindications to immunotherapy, or who cannot attend study visits at the listed sites are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, subcutaneous delivery could offer a more convenient and potentially better-tolerated way to give blinatumomab while keeping its anti-leukemia activity.

How similar studies have performed: Intravenous blinatumomab has demonstrated clinical benefit in relapsed/refractory and MRD-positive B-ALL, but subcutaneous administration is a newer approach with limited prior clinical data.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Ph-IIC, Dose Escalation and Dose Expansion: Aged 18 years or older (or same or greater than legal age within the country if it is older than 18 years).
* Ph-IIRa and Ph-IIMa: Aged ≥ 17 years at time of informed consent.
* Ph-IIRb and Ph-IIMb: Age ≥ 12 years and \< 17 years at time of informed consent.
* Ph-IIR, Ph-IIC, Dose escalation, Dose Expansion: Participants with R/R B-precursor ALL.
* Relapsed or Refractory B-precursor ALL at any time after first salvage therapy.
* Relapsed B-precursor ALL at any time after allogenic hematopoietic stem cell transplant (HSCT).
* Ph-IIR, Ph-IIC, Dose escalation, Dose expansion: Greater than or equal to 5% blasts in the Bone Marrow per local assessment.
* Ph-IIM: B-precursor ALL and bone marrow blasts (BMB) ≥ 0.01% and \< 5% per local assessment.
* Ph-IIM: Availability of an appropriate archival BM specimen from initial or relapse diagnosis and the screening BM sample.
* Participants aged ≥ 18 years: Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
* Participants aged 16 to \< 18 years old: Karnofsky Performance Score ≥ 50%.
* Participants aged \< 16 years old: Lansky Performance Score ≥ 50%.
* Any Ph+ participant intolerant or refractory to prior tyrosine kinase inhibitors (TKIs) are eligible.
* Ph-IIM: BM function as follows:

  * Absolute Neutrophil Count (ANC) ≥ 500/μL
  * Platelet count ≥ 50 000/μL (transfusion permitted)
  * Hemoglobin level ≥ 9 g/dL (transfusion permitted)

The above is a summary, other inclusion criteria details may apply.

Exclusion Criteria:

* Active ALL in the central nervous system (CNS). Presence of greater than 5 white blood cells per cubic millimeter in cerebrospinal fluid (CSF) with lymphoblasts present and/or clinical signs of CNS leukemia. If CSF leukemia is present subjects will have to receive intrathecal therapy and have documented negative CSF prior to enrolling.
* History or presence of clinically relevant CNS pathology (excluding headache) such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, psychosis or severe (≥ grade 3) CNS events including immune effector cell-associated neurotoxicity syndrome (ICANS) from prior chimeric antigen receptor T-cell (CAR T) or other T cell engager therapies.
* Isolated Extramedullary (EM) Disease.
* For Ph-IIM only: Current EM disease or presence of circulating leukemia blasts.
* Current autoimmune disease or history of autoimmune disease with potential CNS involvement.
* Active acute or chronic graft versus host disease requiring systemic treatment with immunosuppressive medication.
* Symptoms and/or signs that indicate an acute or uncontrolled chronic infection, any other disease or condition that could be exacerbated by the treatment or would complicate protocol compliance.
* Testicular leukemia.
* History of malignancy (with certain exceptions) other than ALL within 3 years prior to start of protocol-specified therapy.
* Allogeneic HSCT within 12 weeks before the start of protocol-specified therapy.
* Cancer chemotherapy within 2 weeks before the start of protocol-specified therapy (with certain exceptions).
* Immunotherapy within 4 weeks before start of protocol-specified therapy.
* Prior failed cluster of differentiation (CD19) directed therapy such as prior blinatumomab or CD19 CAR T cells will be allowed (with demonstrated continued CD19+ expression), if treatment ended more than 4 weeks prior to start of protocol therapy and no prior CNS complications.
* Currently receiving treatment in or less than 30 days or 5 half-lives since ending treatment on another investigational study(ies).
* Abnormal screening laboratory parameters.
* Female participant: Pregnant or breastfeeding or planning to become pregnant or donate eggs, or expected to breastfeed during treatment and for 96 hours after the last dose of investigational product (SC blinatumomab).

The above is a summary, other exclusion criteria details may apply.

Where this trial is running

Clovis, California and 108 other locations

+59 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions B Cell Precursor Acute Lymphoblastic LeukemiaR/R B-ALLMRD+ B-ALLRelapsedRefractoryMinimal Residual DiseaseAMG 103Blinatumomab
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.