Blinatumomab for Treatment of R/R or MRD-positive CD19-Positive MPAL

NCT ID: NCT04827745

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-11
• Study Completion Date: 2025-05-22

Brief Summary

This is a research study to find out if a drug called blinatumomab is effective for treating patients with relapsed or refractory (R/R) or measurable residual disease (MRD) CD19-positive mixed phenotypic acute leukemia (MPAL). Measurable Residual Disease (MRD) means that there are a small number of cancer cells remaining after treatment

Detailed Description

This is a multicenter, non-randomized, open-label, phase II study evaluating the efficacy of blinatumomab to achieve the following objectives:

1. The best morphologic response after the first two cycles of therapy in subjects with morphologic R/R CD19-positive MPAL

2. MRD-negativity in subjects with CD19-positive MPAL in CR, or CRh, or CRi or CRp after receiving at least one chemotherapy block of standard ALL or AML treatment with MRD-positivity at a level of ≥ 0.1% using an assay with a minimum sensitivity of 0.01%

The trial consists two groups (Group A and B) and three phases ( induction, consolidation and maintenance) of therapy. Subject will receive study drug blinatumomab by continuous IV infusion (CIV). Each treatment cycle consists of 28 days of blinatumomab CIV followed by a 14±3 days treatment-free interval for induction, 28±3 days treatment-free interval for consolidation, and 56±3 days treatment-free interval for maintenance

Blinatumomab is approved by Food and Drug Administration [FDA] and European Medicines Agency [EMA] for use in people with another type of acute leukemia called acute lymphoblastic leukemia (ALL) but not MPAL.

Conditions

Mixed Phenotype Acute Leukemia (MPAL); Measurable Residual Disease (MRD)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Subjects with R/R CD19-positive MPAL

Cohort A: Evaluate the efficacy of blinatumomab to achieve the best morphologic response after the first two cycles of therapy in subjects with morphologic R/R CD19-positive MPAL

• The treatment of blinatumomab consists of induction, consolidation and maintenance therapy
• Subject will receive study drug blinatumomab by continuous IV infusion (CIV)
• Each treatment cycle consists of 28 days of blinatumomab CIV followed by a 14±3 days treatment-free interval for induction, 28±3 days treatment-free interval for consolidation, and 56±3 days treatment-free interval for maintenance
• The initial dose of blinatumomab is 9 mcg/day for 7 days. The target dose for rest of treatment is 28 mcg/day

Group Type: EXPERIMENTAL

BLINCYTO (Blinatumomab)

Intervention Type: DRUG

Blinatumomab (BLINCYTO , AMG 103, formerly also known as MT103 or bscCD19xCD3) is a novel single chain antibody construct in the class of the bispecific T-cell engager (BiTE®). Blinatumomab directs CD-3 positive effector memory T cells to CD19-positive target cells (Hoffmann et al, 2005; Dreier et al, 2002). The targeted CD19 antigen is constitutively expressed on normal B cells throughout a person's lifetime (Smet et al, 2011) and is highly conserved in B-cell malignancies (Tedder, 2009; Wang et al, 2012).

Subjects with CD19-positive MPAL in CR/CRh/CRi/CRp and detectable MRD

Cohort B: Evaluate the efficacy of blinatumomab to achieve MRD-negativity in subjects with CD19-positive MPAL in CR, or CRh, or CRi or CRp after receiving at least one chemotherapy block of standard ALL or AML treatment with MRD-positivity at a level of ≥ 0.1% using an assay with a minimum sensitivity of 0.01%

• The treatment of blinatumomab consists of induction, consolidation and maintenance therapy
• Subject will receive study drug blinatumomab by continuous IV infusion (CIV)
• Each treatment cycle consists of 28 days of blinatumomab CIV followed by a 14±3 days treatment-free interval for induction, 28±3 days treatment-free interval for consolidation, and 56±3 days treatment-free interval for maintenance.
• The dose of blinatumomab is 28 mcg/day

Group Type: EXPERIMENTAL

BLINCYTO (Blinatumomab)

Intervention Type: DRUG

Blinatumomab (BLINCYTO , AMG 103, formerly also known as MT103 or bscCD19xCD3) is a novel single chain antibody construct in the class of the bispecific T-cell engager (BiTE®). Blinatumomab directs CD-3 positive effector memory T cells to CD19-positive target cells (Hoffmann et al, 2005; Dreier et al, 2002). The targeted CD19 antigen is constitutively expressed on normal B cells throughout a person's lifetime (Smet et al, 2011) and is highly conserved in B-cell malignancies (Tedder, 2009; Wang et al, 2012).

Interventions

BLINCYTO (Blinatumomab)

Blinatumomab (BLINCYTO , AMG 103, formerly also known as MT103 or bscCD19xCD3) is a novel single chain antibody construct in the class of the bispecific T-cell engager (BiTE®). Blinatumomab directs CD-3 positive effector memory T cells to CD19-positive target cells (Hoffmann et al, 2005; Dreier et al, 2002). The targeted CD19 antigen is constitutively expressed on normal B cells throughout a person's lifetime (Smet et al, 2011) and is highly conserved in B-cell malignancies (Tedder, 2009; Wang et al, 2012).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects must have histologically or cytologically confirmed R/R CD19-positive MPAL based on the WHO criteria, OR CD19-positive MPAL in CR/CRh/CRi/CRp after at least one chemotherapy block of standard ALL or AML therapy with detectable MRD ≥ 0.1%. Primary refractory MPAL is defined by absence of CR/CRh/CRi/CRp after at least one cycle of standard AML/ALL induction therapy. A patient has relapsed MPAL if they achieved a CR/CRh/CRi/CRp after induction therapy (CR1) and has then relapsed during, or after continuation of therapy.
• Age 18 years and older
• 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 all immunosuppressive therapy
• Previous cytotoxic chemotherapy (except for hydroxyurea) must have been completed at least 2 weeks prior to day 1 of treatment on the study. Subjects with hematologic malignancies are expected to have hematologic abnormalities at study entry.
• ECOG performance status < 3
• 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
• Subjects with a history of CNS leukemia must be clinically stable with a flow cytometric clear CSF in the 2 weeks prior to day 1 of blinatumomab administration. Subjects with history of CNS leukemia in Cohort A should have received one dose of intrathecal chemotherapy in the 4 weeks prior to day 1 of blinatumomab administration. Subject can receive subsequent prophylactic intrathecal chemotherapy.
• Female subjects of childbearing potential must have a negative pregnancy test
• 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

Exclusion Criteria

• Subjects receiving any other investigational agents, or concurrent chemotherapy, radiation therapy, or immunotherapy not including corticosteroids or hydroxyurea
• Subjects with acute leukemia with any of the following cytogenetic abnormalities:

t(15;17)(q24;q21) PML/RARA, t(8;21)(q22;q22) RUNX1/RUNX1T1, inv(16)(p13q22)/t(16;16)(p13;q22) CBFB-MYH11

• A history or presence of clinically relevant CNS pathology (e.g., as epilepsy, paresis, aphasia, stroke, severe brain injuries, dementia, cerebellar disease, psychosis)
• Hyperleukocytosis with > 50,000 blasts/µL. Hydroxyurea for blast count control is permitted before starting treatment and up to maximum of 10 days after starting treatment on the study. The WBC need not reach 50,000/µL to start hydroxyurea during protocol; the decision to start hydroxyurea during this time is at the discretion of the treating physician
• Active, uncontrolled infection; subjects with infection under active treatment and controlled with antimicrobials are eligible
• Pregnant women
• Uncontrolled undercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled active seizure disorder, or psychiatric illness/social situations that per site Principal Investigator's judgment would limit compliance with study requirements

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Vu Duong, MD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland, Baltimore

Locations

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Countries

United States

Other Identifiers

2099GCCC ; HP-00094794

Identifier Type: -

Identifier Source: org_study_id