Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL)
Condition: Non-Hodgkin Lymphoma; Burkitt's Lymphoma; Chronic Lymphocytic Leukemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Marginal Zone; Waldenstrom Macroglobulinemia; Primary Mediastinal B-cell Lymphoma
MeSH terms: Burkitt Lymphoma; Lymphoma; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Waldenstrom Macroglobulinemia; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell
Intervention: ADCT-402
Intervention description: intravenous infusion
Intervention MeSH terms: Loncastuximab tesirine
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 183.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Loncastuximab tesirine

Summary:

      This study evaluates ADCT-402 in participants with Relapsed or Refractory B-cell Lineage Non
      Hodgkin Lymphoma (B-NHL). Participants will participate in a dose escalation phase (Part 1)
      and dose expansion (Part 2). In Part 2, participants will receive the dose level identified
      in Part 1.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female participants, ages 18 years or older with pathologically confirmed
             relapsed or refractory B-cell lineage NHL who have failed or are intolerant to
             established therapy, or for whom no other treatment options are available.

          -  Refractory or relapsed B-cell NHL (per World health Organization [WHO] Classification
             system).

          -  Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block.

          -  Measurable disease, as defined by the 2014 Lugano Classification.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

          -  Absolute neutrophil count (ANC) ≥1000/μL.

          -  Platelet count of ≥75000/μL.

          -  Hemoglobin ≥9.0 g/dL without transfusion within the 2 weeks prior to Day 1.

          -  Serum/plasma creatinine ≤1.5 mg/dL.

          -  Serum/plasma alkaline phosphatase, alanine aminotransferase (ALT), and aspartate
             aminotransferase (AST) ≤2 times the upper limit of normal (ULN); ≤ 5 times ULN if
             there is liver or bone involvement.

          -  Total serum/plasma bilirubin ≤1.5 times ULN.

          -  Negative blood or urine beta-human chorionic gonadotropin (β-HCG) pregnancy test
             within 7 days prior to Day 1 for women of childbearing potential.

          -  Males, and female participants who are biologically capable of having children, must
             agree to use a medically acceptable method of birth control.

        Exclusion Criteria:

          -  Participants who have any option for other treatment for B-cell NHL at the current
             state of disease.

          -  Active graft-versus-host disease.

          -  Autologous or allogenic transplant within the 60 days prior to the Screening visit.

          -  Known history of immunogenicity or hypersensitivity to a CD19 antibody.

          -  Evidence of myelodysplasia or myeloid leukemia by morphology, immunostains, flow
             cytometry, or cytogenetics on a bone marrow aspirate or biopsy.

          -  Known history of positive serum human ADA.

          -  Active autoimmune disease, motor neuropathy considered of autoimmune origin, and other
             central nervous system (CNS) autoimmune disease.

          -  Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen
             (HbsAg), or antibody to hepatitis C virus (anti-HCV).

          -  History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.

          -  Pregnant or breastfeeding women.

          -  Significant medical comorbidities, including uncontrolled hypertension (diastolic
             blood pressure greater than 115 mm Hg), unstable angina, congestive heart failure
             (greater than New York Heart Association class II), severe uncontrolled ventricular
             arrhythmias, or electrocardiographic evidence of acute ischemia, poorly controlled
             diabetes, severe chronic pulmonary disease, coronary angioplasty, or myocardial
             infarction within 6 months prior to screening, or uncontrolled atrial or ventricular
             cardiac arrhythmias.

          -  Use of any other experimental medication(s) within 14 days or 5 half-lives but in no
             case less than 14 days prior to start of study treatment on Cycle 1, Day 1, except if
             approved by Sponsor.

          -  Steroid use equivalent to greater than 20 mg of prednisone within 4 weeks (28 days)
             prior to Day 1.

          -  Major surgery, chemotherapy, systemic therapy (excluding steroids hydroxyurea
             steroids, and any targeted small molecules or biologics), or radiotherapy, within 14
             days or 5 half-lives (whichever is shorter) prior to Cycle 1, Day 1 treatment, except
             if approved by the Sponsor.

          -  Failure to recover (to Common Terminology Criteria for Adverse Events [CTCAE] Grade 0
             or Grade 1) from acute non hematologic toxicity (except all grades alopecia or Grade 2
             or lower neuropathy), due to previous therapy, prior to Screening.

          -  Congenital long QT syndrome or a corrected QTc interval ≥450 ms at the Screening
             visit.

          -  Active second primary malignancy other than non-melanoma skin cancers, non-metastatic
             prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the
             breast, or other malignancy determined not be exclusionary.

          -  Any other significant medical illness, abnormality, or condition that would make the
             participant inappropriate for study participation or put the participant at risk.