blinatumomab for treatment of r/r or mrd-positive cd19-positive mpal

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

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

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