CAPILANO: This phase II trial is evaluating the effectiveness of an intravenous drug (Blinatumomab) in treating patients with High-risk Diffuse Large B-cell Lymphoma following an autologous Hematopoietic Stem-cell TransplantationA Phase 2 Open-Label Study to Determine the Effect of Blinatumomab on Minimal Residual Disease in Subjects With High-risk Diffuse Large B-cell Lymphoma Post-autologous Hematopoietic Stem-cell Transplantation

Inclusion

Inclusion Criteria - Part 1

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures or subject's legally acceptable representative has provided informed consent prior to any study-specific activities/procedures being initiated when the subject has any kind of condition that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent.
• Age ≥ 18 at time of informed consent
• Biopsy-proven DLBCL excluding DLBCL that represents transformation of indolent non-Hodgkin's lymphoma (NHL) Note: Lymphoblastic Lymphoma and Burkitt Lymphoma histology are not eligible

• Subject has ≥ 1 characteristic feature of high-risk DLBCL:

  • High-risk first complete remission (defined as interim positron emission tomography - computed tomography (PET-CT) positive or < complete remission to frontline chemotherapy AND achieved complete remission to platinum-containing salvage)
  • Relapse within 1 year of diagnosis
  • Secondary age-adjusted international prognostic index > 1
  • Partial response/partial metabolic response after minimum of 2 cycles of platinum-containing salvage chemotherapy
  • C-myc rearrangement
• aHSCT with high-dose chemotherapy following first (or later) salvage treatment.
• PET-CT negative (Deauville score ≤ 3) 90 days (± 30 days) post aHSCT
• Available relapsed and/or diagnostic pathology formalin-fixed paraffin-embedded (FFPE) tumor block or slide samples at the time of enrollment including the successful identification of malignant clone sequences by the central laboratory.
• MRD plasma sample collected ≤ 3 weeks after the post aHSCT PET-CT scan
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

• Adequate organ function determined ≤ 3 weeks prior to enrollment defined as follows:

  • Hematological:

Absolute neutrophil count (ANC) ≥ 1.0 x 109/L Platelet count ≥ 75 x 109/L Hemoglobin ≥ 8 g/dL

• Renal:

Creatinine clearance ≥ 50 mL/min Cockcroft-Gault equation

• Hepatic:

Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) Total bilirubin < 2 x ULN (unless Gilbert's Disease or if liver involvement with lymphoma)

• Subject will be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject's and investigator's knowledge including but not limited to:
• Completion of up to a 24-month run-in period

• Completion of all regularly scheduled study visits including blood draws for MRD assessment, clinical disease state assessment, PET-CT scans (ie, at time of MRD positivity or relapse), assignment to treatment with blinatumomab

  • Other Inclusion criteria may apply. See "Inclusion and Exclusion criteria - Part 2".

Inclusion Criteria - Part 2

• MRD-positive assessment (by NGS analysis) at enrollment or at any time during the run-in 1 period
• PET-CT negative (defined by Deauville criteria ≤ 3) at run-in 2 performed ≤ 3 weeks from MRD test result available to the site at run-in 1. Historical PET-CT are allowed if performed ≤ 6 weeks from day 1 (first dose of blinatumomab) and subject has no clinical signs or symptoms suggestive of disease progression (eg, increase in lactate dehydrogenase [LDH] not otherwise explained)

• Adequate organ function determined ≤ 7 days prior to treatment assignment with blinatumomab as follows:

  • Hematological:

ANC ≥ 1.0 x 109/L Hemoglobin ≥ 8 g/L Platelet count ≥ 75 x 109/L

• Renal:

Creatinine clearance ≥ 50 mL/min Cockcroft-Gault equation

• Hepatic:

AST and ALT < 3 x ULN Total bilirubin < 2 x ULN (unless Gilbert's Disease or if liver involvement with lymphoma)