blinatumomab versus standard of care chemotherapy in patients with relapsed or refractory acute lymphoblastic leukemia (all)

Conditions: Relapsed/Refractory B-precursor Acute Lymphoblastic Leukemia

Summary: the primary objective was to evaluate the effect of blinatumomab on overall survival when compared to standard of care (soc) chemotherapy.

adults with relapsed/refractory b-cell precursor all were randomized in a 2:1 ratio to receive blinatumomab or 1 of 4 pre-specified, investigator-chosen, soc chemotherapy regimens. randomization was stratified by age (\< 35 years vs ≥ 35 years of age), prior salvage therapy (yes vs no), and prior allogeneic hsct (yes vs no) as assessed at the time of consent. the study consisted of up to a 3-week screening and pre-phase period, a treatment period consisting of induction with 2 cycles of either blinatumomab or soc chemotherapy, a consolidation phase of up to 3 additional cycles of protocol-specified therapy, and a maintenance phase for up to an additional 12 months with protocol-specified therapy. a safety follow-up visit 30 days after the last dose of protocol-specified therapy and a long-term follow-up period were included. the long-term follow-up part of the study was discontinued prematurely based on a recommendation from the data monitoring committee (dmc) that the study be stopped for benefit.

Eligibility criteria:
* subjects with philadelphia negative b-precursor all, with any of the following: * refractory to primary induction therapy or refractory to salvage therapy, * in untreated first relapse with first remission duration \<12 months * in untreated second or greater relapse * relapse at any time after allogeneic hsct * subject has received intensive combination chemotherapy for the treatment of all for initial treatment or subsequent salvage therapy. * greater than 5% blasts in the bone marrow * eastern cooperative oncology group (ecog) performance status ≤ 2 exclusion criteria * malignancy other than all within 5 years before blinatumomab treatment, except for adequately treated selected cancers without evidence of disease * diagnosis of burkitt's leukemia according to world health organization classification, or human immunodeficiency virus (hiv), hepatitis b or c, or other clinically significant disorder * current relevant central nervous system (cns) pathology or known or suspected cns involvement * isolated extramedullary disease * current autoimmune disease or history of autoimmune disease with potential cns involvement * autologous hsct within 6 weeks or allogeneic hsct within 12 weeks before blinatumomab treatment, or eligibility for allogeneic hsct at the time of enrollment * active acute grade 2 to 4 graft versus host disease (gvhd) according to glucksberg et al (1974) criteria that required systemic treatment to prevent or treat gvhd 2 weeks before blinatumomab treatment * known exclusion criteria to investigator choice of soc chemotherapy (per package insert) * cancer chemotherapy or radiotherapy with 2 weeks, or immunotherapy (included cd19 therapy) within 4 weeks of protocol-specified therapy * abnormal laboratory values (alanine or aspartate transaminase \[alt or ast\] or alkaline phosphatase \[alp\] ≥ 5 × upper limit of normal \[uln\]; total bilirubin or creatinine ≥ 1.5 × uln), or calculated creatinine clearance \< 60 ml/min.

Keywords: relapsed; refractory; b-precursor; acute lymphoblastic leukemia; philadelphia negative; all; blinatumomab; leukemia; standard of care; soc