Subcutaneous blinatumomab treatment for adults with CD19-positive mixed phenotype acute leukemia

A Multicenter Phase II Study of Subcutaneous Blinatumomab for Treatment of Adult Patients With CD19-Positive Mixed Phenotype Acute Leukemia (MPAL)

This trial tests whether giving blinatumomab under the skin can help adults with CD19-positive mixed phenotype acute leukemia, including older or unfit newly diagnosed patients, those with measurable residual disease after remission, and those with relapsed or refractory disease.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 78 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: West Virginia University (other)
• Drugs / interventions: blinatumomab, chemotherapy, immunotherapy, radiation
• Locations: 1 site (Morgantown, West Virginia)
• Trial ID: NCT07222579 on ClinicalTrials.gov

What this trial studies

This is a multicenter, non-randomized, open-label phase II study of subcutaneous blinatumomab in adults with CD19-positive MPAL. Participants are enrolled into one of three cohorts: newly diagnosed older or unfit patients (Cohort A), patients in remission but with measurable residual disease ≥0.1% (Cohort B), and patients with morphologic relapsed or refractory disease (Cohort C). The regimen uses repeated subcutaneous doses with scheduled clinic visits for safety monitoring, response assessments including MRD testing, and supportive care; select post–allo-HSCT patients are eligible under protocol conditions. Primary endpoints target efficacy within each cohort (clinical response or MRD clearance) alongside collection of safety and tolerability data.

Who should consider this trial

Good fit: Adults with CD19-positive MPAL who are newly diagnosed and either ≥75 years or medically unfit for intensive chemotherapy, patients in remission with MRD ≥0.1%, or patients with relapsed/refractory disease after prior therapy are the intended candidates.

Not a fit: Patients without CD19 expression, those with uncontrolled graft-versus-host disease, or those with serious uncontrolled infections or active severe neurologic symptoms may not receive benefit from this treatment.

Why it matters

Potential benefit: If successful, subcutaneous blinatumomab could provide a less-intensive, outpatient-friendly option that induces remissions or clears MRD in CD19-positive MPAL patients who cannot tolerate intensive chemotherapy.

How similar studies have performed: Intravenous blinatumomab has demonstrated activity in CD19-positive B-cell acute leukemias and can clear MRD, but subcutaneous administration and specific use in MPAL remain relatively novel with limited prior data.

Eligibility criteria

* Inclusion Criteria:
* General Criteria for all three Cohorts

  * Subjects must have histologically or cytologically confirmed MPAL based on 2022 WHO criteria
  * Subjects who have undergone allo-HSCT are eligible if they are ≥ 4 weeks post stem cell infusion, have no evidence of GVHD \> Grade 2, and are at least ≥ 1 week off of immunosuppressive therapy. Per FDA recommendation, patients should be off of calcineurin inhibitors (CNIs) for at least 4 weeks before receiving blinatumomab
  * Subjects with a CNS leukemia must be clinically stable (i.e., asymptomatic with no focal neurological signs and symptoms, or signs and symptoms unchanged over 4 weeks with no \> grade 2 manifestations) with a flow cytometric clear CSF in the 2 weeks prior to day 1 of SC-blinatumomab administration.
  * Ability to understand and willingness to sign a written informed consent document
  * Agree to comply with the study requirements and agree to come to the clinic/hospital for required study visits
  * Subjects with hematologic malignancies are expected to have hematologic abnormalities at study entry
* Specific Criteria for Cohort A

  o Subjects should be ineligible for available induction therapy either if they are 75 years of age or older or if they have at least one of the following coexisting conditions precluding intensive chemotherapy: a history of CHF for which treatment is warranted or a report of EF ≤50% in the last 12 months, a history of chronic stable angina, a report of DLCO of ≤65% or FEV1 ≤65% in the last 12 months, ECOG performance status 3 or 4, Charlson comorbidity index (CCI) ≥3.
* Specific Criteria for Cohort B

  * CD19+ MPAL in CR/CRh/CRi after at least one line of treatment with MRD positivity at a level of ≥0.1% using an assay with a minimum sensitivity of 0.01%.
  * ECOG performance status ≤2
  * Subjects must have organ function as below:

    * Direct bilirubin ≤ 2.5 mg/dL
    * AST/ALT/Alkaline phosphatase ≤ 5 X institutional upper limit of normal
    * Serum creatinine ≤ 3 mg/dL
* Specific Criteria for Cohort C

  * Confirmed R/R CD19+ MPAL
  * Previous cytotoxic chemotherapy (except for hydroxyurea) must have been completed by 5 half-lives of the drug(s) prior to day 1 of SC-blinatumomab. Per FDA recommendation, patients should have recovered to no more than Grade 1 toxicities from prior chemotherapy.
  * ECOG performance status ≤2
  * Subjects must have organ function as below:

    * Direct bilirubin ≤ 2.5 mg/dL
    * AST/ALT/Alkaline phosphatase ≤ 5 X institutional upper limit of normal
    * Serum creatinine ≤ 3 mg/dL
* Exclusion Criteria:
* Criteria for all three Cohorts

  * Subjects receiving any other investigational agents, or concurrent chemotherapy, radiation therapy, or immunotherapy for cancer treatment not including corticosteroids or hydroxyurea
  * Active, uncontrolled infection; subjects with infection under active treatment and controlled with antimicrobials are eligible

Where this trial is running

Morgantown, West Virginia

• West Virginia University Cancer Institute — Morgantown, West Virginia, United States (RECRUITING)

Study contacts

• Principal investigator: Ashkan Emadi, MD — WVU Cancer Institute
• Study coordinator: Ashkan Emadi, MD

Conditions: CD19 Positive, Mixed Phenotype Acute Leukemia