Clinical trial NCT04827745: Blinatumomab for Treatment of R/R or MRD-positive CD19-Positive MPAL
Official title: A Multicenter Phase II Study of Blinatumomab for Treatment of Adult Patients With Morphologic Relapsed/Refractory or Measurable Residual Disease (MRD) CD19-Positive Mixed Phenotype Acute Leukemia (MPAL)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Mixed Phenotype Acute Leukemia (MPAL)
Measurable Residual Disease (MRD)
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
First posted: 2021-04-01
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cohort A: Subjects with R/R CD19-positive MPAL

CohortB: Subjects with CD19-positive MPAL in complete remission and detectable MRD
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Cohort A response rate
timeFrame: through study completion, an average of 1 year
measure: Cohort B response rate
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Cohort A survival
timeFrame: 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
measure: Cohort B survival
timeFrame: 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:
measure: CD 19 measurement
timeFrame: through study completion, an average of 1 year
measure: CD3-positive measurement
timeFrame: through study completion, an average of 1 year
measure: Leukemic blasts evaluation
timeFrame: through study completion, an average of 1 year
measure: Subject response evaluation
timeFrame: through study completion, an average of 1 year
Locations:
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
Study officials:
affiliation: University of Maryland, Baltimore
name: Vu Duong, MD
role: PRINCIPAL_INVESTIGATOR
References: