A Phase 1b Open-Label Study Investigating the Safety and Pharmacokinetics of Administration of Subcutaneous Blinatumomab for the Treatment of Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma
Condition: Non-Hodgkin's Lymphoma
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: blinatumomab
Intervention description: Blinatumomab used as both continuous IV infusion and subcutaneous injection
Intervention MeSH terms: Blinatumomab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 35.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Primary Objective:

      • To evaluate the safety and tolerability of subcutaneous (SC) blinatumomab dose
      administrations

      Secondary Objectives:

        -  To determine pharmacokinetics (PK) with continuous intravenous (cIV) and SC
           administrations

        -  To estimate the maximum tolerated dose (MTD) tested for blinatumomab administered
           subcutaneously

        -  To determine the incidence of anti-blinatumomab antibody formation following SC
           administration

        -  To evaluate efficacy response following treatment with SC blinatumomab administration

      Exploratory Objective:

        -  To determine the pharmacodynamics (PD) time profiles for B-and T-lymphocytes as well as
           cytokine profiles during SC administration

        -  To evaluate efficacy response following treatment with SC blinatumomab administration
           using Lugano criteria if positron emission tomography-computed tomography (PET/CT) is
           used for evaluation
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject or subject's legally acceptable representative has provided informed consent.

          -  Age greater than or equal to 18 years old at the time of informed consent

          -  Subjects must have a histologically determined B cell NHL subtype as defined in the
             bullets below.

        In addition, they must have disease that is primary refractory after initial therapy or
        have relapsed disease.

          -  Follicular Lymphoma I, II, IIIA

          -  Marginal zone lymphoma (extranodal, nodal or splenic). Subjects with gastric mucosa-

          -  associated lymphoid tissue must have progressed after Helicobacter pylori therapy and

          -  radiation. Subjects with splenic marginal zone lymphoma must have prior splenectomy.

          -  Lymphoplasmocytic lymphoma

          -  Mantle cell lymphoma ([MCL] with the exception of aggressive MCL, defined as Ki67 >
             30%,

          -  or blastoid histology)

          -  Small lymphocytic lymphoma

             • Subjects without standard therapy alternatives, or contraindicated for standard
             therapy by investigator, or subjects unwilling to receive standard therapy. Disease
             status must be 1 of the following:

          -  Primary refractory (at least 1 prior line of therapy)

          -  Relapsed within 1 year of first response

          -  Responded to initial therapy for ≥ 1 year and relapsed after 2 or more lines of
             therapy, including an anti-CD20 monoclonal antibody

               -  Measurable disease that has not been previously irradiated on positron emission
                  tomography- computed tomography (PET-CT), or computed tomography (CT), of at
                  least 1.5 cm within the last 21 days before the start of IP treatment.

               -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal
                  to 2

               -  Life expectancy greater than or equal to 3 months as determined by treating
                  physician.

               -  Subjects must have adequate organ and marrow at screening as defined below:

          -  peripheral neutrophils >500/µL prior to start of treatment

          -  hemoglobin ≥8 g/dL

          -  Platelets greater than or equal to 50,000 mcL

          -  aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) < 5 × upper limit of
             normal (ULN

          -  Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN)

          -  Creatinine clearance greater than or equal to 50 mL/min (Cockcroft-Gault)

        Exclusion Criteria:

          -  Currently receiving treatment in another investigational device or drug study, or less
             than 30 days between ending treatment on another investigational device or drug
             study(ies) and start of IP treatment. Other investigational procedures while
             participating in this study are excluded.

          -  Known hypersensitivity to immunoglobulins or any other component of the study drug

          -  Subject likely to not be available to complete all protocol required study visits or
             procedures to the best of the subject and investigator's knowledge

          -  History or 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.

          -  Subjects who have had treatments with anti-cancer agents including rituximab or
             obinutuzumab and/or other monoclonal antibody or radioimmunotherapy within 6 weeks
             before the starting IP treatment.

          -  Autologous stem cell transplantation within 12 weeks before the starting IP treatment
             or past history of allogeneic stem cell transplantation.

          -  Subjects who have received anti-CD 19 targeted therapies, chimeric antigen receptor
             T-cell or other cellular therapies for the treatment of their lymphoma .

          -  Subjects with suspected or known brain metastases should be excluded from this
             clinical study because of their poor prognosis and because they often develop
             progressive neurologic dysfunction that would confound the evaluation of neurologic
             and other adverse events.

          -  Infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis
             B virus or hepatitis C virus.

          -  History of or current relevant central nervous system pathology such as epilepsy,
             recurrent seizures, paresis, aphasia, apoplexia, severe brain injuries, cerebellar
             disease, organic brain syndrome or psychosis.

          -  History of malignancy other than their lymphoma with the exception of:

               -  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 maligna 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 noninvasive carcinoma or carcinoma in
                  situ.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or
             uncontrolled systemic fungal bacteria, viral, or other infection, symptomatic
             congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric
             illness/social situations that would limit compliance with study requirements.

          -  A female who is pregnant or breastfeeding or planning to become pregnant or breastfeed
             during treatment and for an additional 48 hours (Period 1) or 96 hours (Period 2),
             respectively, after the last dose of blinatumomab (Female subjects of childbearing
             potential should only be included in the study after a confirmed menstrual period and
             a negative highly sensitive urine or serum pregnancy test).

          -  A female of childbearing potential unwilling to use highly effective method of
             contraception during treatment and for an additional 48 hours (Period 1) or 96 hours
             (Period 2), respectively, after the last dose of blinatumomab.