Safety and Efficacy of Blinatumomab in Adults With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma

A phase 2, multicenter, open-label, single arm clinical trial in adults with newly diagnosed aggressive high-risk DLBCL.

The safety profile of blinatumomab after frontline rituximab (R)-chemotherapy, consisting of either R-CHOP (14 or 21) (rituximab/cyclophosphamide/doxorubicin/vincristine/prednisone) or R-DA-EPOCH (rituximab and dose adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), or R-CHOEP (rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide), will be determined. The study will consist of a screening period of up to 14 days, a standard of care (SOC) R-chemotherapy run-in period of approximately 21 weeks, a 12 to 16 week blinatumomab treatment period, a 30-day safety follow-up visit, and a long-term follow-up period that begins after the safety follow-up visit is completed until 1 year from the first dose blinatumomab.

Eligibility Criteria:
Inclusion criteria:

* Subject has provided informed consent prior to initiation of any study-specific activities/procedures
* Age ≥ 18 at time of informed consent
* Subject must have untreated histologically proven high-risk DLBCL defined by atleast one of the following:

  * International Prognostic Index (IPI) for Diffuse Large B-cell Lymphoma 3 to 5 (representing high intermedidate - high ratings),
  * Double-hit or higher or double protein expression
* Eastern Cooperative Oncology Group performance status ≤ 2.
* Subject meets the criteria per investigator's institution to receive standard of care (SOC) rituximab-chemotherapy (ie, R-CHOP \[14 or 21\] or R-DA-EPOCH or R-CHOEP) of 6 cycles. Subjects may be enrolled on study prior to cycle 1 or cycle 2 of SOC R-chemotherapy
* Adequate organ and bone marrow function determined within 14 days prior to enrollment defined as:

  * Hematological: Absolute neutrophil count ≥1\*10\^9/L; Platelet count ≥75\*10\^9/L;Hemoglobin ≥8g/dL
  * Renal: Creatinine clearance ≥50mL/min;
  * Hepatic: Aspartate aminotransferase/Alanine aminotransferase \<3\*upper limit of normal (ULN); Total bilirubin \<2\*ULN (unless Gilbert's Disease or if liver involvement with lymphoma)
* Subject must have completed 6 cycles of SOC R-chemotherapy and achieved CR, PR or stable disease by PET/CT performed 3 weeks (± 3 days) after cycle 6 of SOC R-chemotherapy. Subjects with progressive disease (PD) are not eligible for treatment with blinatumomab and will end the study.

Exclusion Criteria:

* Clinically relevant central nervous system (CNS) pathology requiring treatment such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and psychosis
* Evidence of CNS involvement with DLBCL at disease evaluation obtained prior to starting blinatumomab
* Current autoimmune disease or history of autoimmune disease with potential of CNS involvement
* Subject has active infection requiring systemic therapy
* Prior anti-CD19 therapies
* Known infection with HIV or chronic infection with hepatitis B virus or hepatitis C virus
* History of other malignancy within the past 3 years with the following exceptions:

  * Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician
  * Adequately treated non-melanoma skin cancer or lentigo malignancy without evidence of disease
  * Adequately treated cervical carcinoma in situ without evidence of disease
  * Adequately treated breast ductal carcinoma in situ without evidence of disease
  * Prostatic intraepithelial neoplasia without evidence of prostate cancer
  * Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ
* Subject has known hypersensitivity to immunoglobulins or any of the products or components to be administered during dosing.
* Subject likely to not 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.
* History/evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
* Females who are pregnant or breastfeeding or planning to become pregnant or breastfeed while receiving blinatumomab and for an additional 48 hours after the last treatment dose of blinatumomab.
* Currently receiving treatment in another investigational device or drug study or less than 30 days since ending treatment on another investigational device or drug study. Other investigational procedures while participating in this study are excluded.