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

NCT04827745 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: 2099GCCC ; HP-00094794
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

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

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Cohort A response rate

  The rate of achievement of CR+CRh after the first 2 cycles of blinatumomab in Cohort A subjects

  through study completion, an average of 1 year

• Cohort B response rate

  The rate of achievement of MRD-negativity (\< 0.01%) after the first 2 cycles of blinatumomab in Cohort B subjects

  through study completion, an average of 1 year

Secondary Outcomes (2)

• Cohort A survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

• Cohort B survival

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Other Outcomes (4)

• CD 19 measurement

  through study completion, an average of 1 year

• CD3-positive measurement

  through study completion, an average of 1 year

• Leukemic blasts evaluation

  through study completion, an average of 1 year

Study Arms (2)

Subjects with R/R CD19-positive MPAL

EXPERIMENTAL

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

Drug: BLINCYTO (Blinatumomab)

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

EXPERIMENTAL

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

Drug: BLINCYTO (Blinatumomab)

Interventions

BLINCYTO (Blinatumomab) 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; Subjects with R/R CD19-positive MPAL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead

Study Sites (1)

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Neoplasm, Residual

Interventions

blinatumomab

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Vu Duong, MD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Cohort A: Subjects with R/R CD19-positive MPAL CohortB: Subjects with CD19-positive MPAL in complete remission and detectable MRD

Study Record Dates

• First Submitted: March 25, 2021
• First Posted: April 1, 2021
• Study Start: June 11, 2021
• Primary Completion: May 22, 2025
• Study Completion: May 22, 2025
• Last Updated: July 3, 2025

Record last verified: 2025-07

Locations

US (1)