Subcutaneous Blinatumomab for Treatment of Adult Patients With CD19-Positive Mixed Phenotype Acute Leukemia (MPAL)

Official title

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

Overview

This is a multicenter, non-randomized, open-label, phase II study evaluating blinatumomab administered subcutaneously in adult subjects with CD19+ MPAL. This trial consists of three cohorts of patients with CD19-positive MPAL, categorized as follows: 1. Cohort A: Newly diagnosed CD19+ MPAL in untreated patients who are either ≥ 75 years of age or have at least one coexisting condition precluding intensive chemotherapy. 2. Cohort B: Patients with CD19+ MPAL who have achieved complete remission (CR, CRh, or CRi) following at least one line of treatment but have detectable measurable residual disease (MRD) at a level of ≥ 0.1%, assessed using an assay with a minimum sensitivity of 0.01%. 3. Cohort C: Patients with CD19+ MPAL with morphologic relapsed or refractory (R/R) disease following at least one prior line of treatment. The Primary Objectives for each cohort are for Cohort A: to evaluate the efficacy of SC-blinatumomab in treatment; for Cohort B: to assess the ability of SC-blinatumomab to achieve MRD-negative CR; for Cohort C: to determine the efficacy of SC-blinatumomab in inducing CR, CRh, or CRi in patients. At specified time points, subjects will undergo the following procedures: collection of informed consent, medical history, demographics, ECOG performance, and physical exam including vital signs as well as neurological examination including examination of writing ability. Subjects will provide samples for complete blood count with differential and blood chemistry profile, have a bone marrow aspiration and biopsy and lumbar puncture will be performed per protocol or if clinically indicated, and/or ECG, Echocardiography, pulmonary function test will be performed only if medically indicated. The subcutaneous treatment will be given in both the inpatient and outpatient setting. For an individual subject the length of participation includes up to a 3-week screening period, up to a 13-month treatment period, and a safety follow-up visit (30 days after the last dose of study treatment), and a follow-up period.

Interventions

• Drug Subcutaneous Blinatumomab
  Blinatumomab will be administered as a subcutaneous (SC) injection.

Primary outcome measures

• Cohort A - Overall Survival [Time frame: Up to 3 years]
• Cohort B - Rate of Complete Remission (CR), Complete Remission with Partial Hematological Recovery (CRh), or Complete Remission with Incomplete Hematological Recovery (CRi) with Minimal Residual Disease (MRD) negativity [Time frame: At completion of 2 cycles (each cycle is 34 days)]
• Cohort C - Rate of Complete Remission (CR) or Complete Remission with Partial Hematological Recovery (CRh) [Time frame: At completion of 2 cycles (each cycle is 34 days)]

Secondary outcome measures (11)

• Cohort A - MRD-negative CR + CRh rate [Time frame: At completion of 2 cycles (each cycle is 34 days)]
• Cohort A - Event-Free Survival (EFS) [Time frame: Up to approximately 3 years]
• Cohort A - Incidence and Severity of Adverse Events (AEs) [Time frame: Up to approximately 1 year]
• Cohort B - Overall Survival [Time frame: Up to approximately 3 years]
• Cohort B - Rate of MRD-negativity (<0.01%) [Time frame: At completion of 1 cycle (cycle is 34 days)]
• Cohort B - Event-Free Survival (EFS) [Time frame: Up to approximately 1 year]
• Cohort B - Incidence and Severity of Adverse Events (AEs) [Time frame: Up to approximately 1 year]
• Cohort C - Overall Survival [Time frame: Up to approximately 3 years]
• Cohort C - Event-Free Survival (EFS) [Time frame: Up to approximately 1 year]
• Cohort C - Incidence and Severity of Adverse Events (AEs) [Time frame: Up to approximately 1 year]
• Overall - Incidence and Severity of Adverse Events (AEs) [Time frame: Up to approximately 1 year]

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• West Virginia University Cancer Institute — Morgantown

Identifiers

NCT: NCT07222579 · 2506170190

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗