Safety and Efficacy of Blinatumomab in Adults With Newly Diagnosed High-risk Diffuse Large B-Cell Lymphoma
Condition: High-risk Diffuse Large B-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: Blinatumomab; Investigator's Choice Chemotherapy; Dexamethasone
Intervention description: Blinatumomab monotherapy was supplied in single-use sterile glass injection vials and administered as an IV infusion.; During the run-in period participants received 6 cycles of standard of care rituximab-chemotherapy dosed per investigator's institution standard as follows:
R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine,prednisone)
R-DA-EPOCH (rituximab and dose adjusted-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) or
R-CHOEP (rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide).; Dexamethasone 20 mg IV: within 1 hour prior to start of treatment in each treatment cycle, and within 1 hour prior to dose-step (increase).
Intervention MeSH terms: Dexamethasone; Blinatumomab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 47.0
Sex: All
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No

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

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.