About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

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

Treatment groups

78 Participants

are divided into 3 treatment groups

Group A: Blinatumomab in Newly Diagnosed CD19+ MPAL, Age ≥ 75 or Unfit for Intensive ChemotherapyExperimental treatment 1 intervention

Group B: Blinatumomab use in CD19+ MPAL in first or second CR/CRh/CRi with detectable MRD ≥0.1%Experimental treatment 1 intervention

Group C: Blinatumomab use in Morphologic R/R CD19+ MPALExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Cohort A - Overall Survival

The Overall Survival (OS) is the time from treatment initiation to death from any cause.

Time frame

Up to 3 years

2

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

The rate of achievement of complete remission (CR/CRh/CRi) with MRD-negativity (\<0.01%) after the first two cycles of therapy with blinatumomab. CR: Bone marrow blasts \<5%; absence of circulating blasts; absence of extramedullary disease; absolute neutrophil count (ANC) ≥1000/µL and platelets ≥100,000/µL; MRD+ or unknown. CR +CRh: Bone marrow blasts \<5%; absence of circulating blasts; absence of extramedullary disease; ANC ≥500/µL AND platelet count ≥50,000/µL. CR +CRi: Bone marrow blasts \<5%; absence of circulating blasts; absence of extramedullary disease; with residual thrombocytopenia (platelet count of \<100,000/µL) OR residual neutropenia (ANC \<1000/µL); not fulfilling criteria for CRh. MRD Negativity: No detectable cancer cells using sensitive tests, with less than 0.01% cancer cells. MRD positivity indicates a higher risk of relapse, while MRD negativity is linked to long-term remission and survival benefits.

Time frame

At completion of 2 cycles (each cycle is 34 days)

3

Cohort C - Rate of Complete Remission (CR) or Complete Remission with Partial Hematological Recovery (CRh)

The rate of achievement of complete remission (CR/CRh) after the first two cycles of therapy with blinatumomab. Complete Remission (CR): No detectable cancer cells in the bone marrow (less than 5% blast cells) and normal blood counts. CRh: No detectable cancer cells, with partial recovery of blood counts (ANC 500-1,000/µL, platelets 50,000-100,000/µL). The rate of achieving these states is calculated by the proportion of patients who reach CR/CRh within a set time. Higher rates of achievement indicate that a larger proportion of participants are responding positively to the treatment, with no detectable cancer cells in their bone marrow and recovery of blood counts.

Time frame

At completion of 2 cycles (each cycle is 34 days)

Secondary outcomes

1

Cohort A - MRD-negative CR + CRh rate

MRD-negative CR + CRh rate is the proportion of participants who achieve either Complete Remission (CR) or Complete Remission with Partial Hematological Recovery (CRh) and also have no detectable minimal residual disease (MRD) in bone marrow. Higher rates of MRD-negative CR + CRh indicate the treatment is highly effective in both inducing remission and reducing the risk of relapse.

Time frame

At completion of 2 cycles (each cycle is 34 days)

2

Cohort A - Event-Free Survival (EFS)

Time from treatment initiation to the earliest occurrence of one of the following events: * Failure to achieve CR, CRh, or CRi after at least two cycles of SC-blinatumomab * Relapse after achieving CR, CRh, or CRi * Initiation of new leukemia-directed therapy due to persistent disease or progression * Death from any cause

Time frame

Up to approximately 3 years

3

Cohort A - Incidence and Severity of Adverse Events (AEs)

The number of AE Incidences including the severity of those events. The descriptions and grading scales found in the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, published on November 27, 2017, will be utilized for AE reporting. The general guidelines for each grade are Grade 1 (Mild), Grade 2 (Moderate), Grade 3 (Severe), Grade 4 (Life-threatening), Grade 5 (Death).

Time frame

Up to approximately 1 year

4

Cohort B - Overall Survival

The Overall Survival (OS)is the time from treatment initiation to death from any cause.

Time frame

Up to approximately 3 years

Other outcomes

1

Overall - Characterization of Antigen Expression

Assess CD19, CD81, and CD21 expression (levels) in leukemic blasts through flow cytometry and/or immunohistochemical staining to evaluate potential biomarkers of treatment response and resistance. High expression levels may correlate with better treatment outcomes, while low or absent expression may indicate resistance.

Time frame

Up to 10 years

2

Overall - Frequency of Cytogenetic Abnormalities Identified by Karyotyping and Fluorescence In Situ Hybridization (FISH)

Percentage of patients with identified cytogenetic abnormalities and will be correlated descriptively with clinical outcomes including treatment response, relapse, and overall survival. The frequency and pattern of disease-specific chromosomal abnormalities detected by conventional karyotyping and fluorescence in situ hybridization (FISH) in leukemic blasts.

Time frame

Up to approximately 10 years

3

Overall - Frequency of Somatic Mutations Identified by Next-Generation Sequencing (NGS) and Polymerase Chain Reaction (PCR)

Percentage of patients with specific genetic alterations and explored for associations with treatment response, relapse patterns, and disease progression. The frequency and spectrum of somatic mutations, gene fusions, or rearrangements detected using next-generation sequencing (NGS) and/or polymerase chain reaction (PCR) in leukemic cells.

Time frame

Up to approximately 10 years

4

Overall - Transplantation and Cellular Therapy Outcomes

The proportion of subjects proceeding to allogeneic hematopoietic stem cell transplantation (alloHSCT) after SC-blinatumomab treatment, assessing their post-transplant outcomes, relapse rates, and overall survival.

Time frame

Up to approximately 3 years

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

About this trial

Eligibility criteria

Qualifiers

Disqualifiers

Trial design

Treatments tested in this trial

Treatment groups

Trial outcomes

Primary outcomes

Secondary outcomes

Other outcomes

Sponsors and contacts