Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Acute Lymphoblastic Leukemia (B-ALL)
Condition: Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
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: 35.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: Loncastuximab tesirine

Summary:

      This study evaluates ADCT-402 in participants with relapsed or refractory B-cell lineage
      acute lymphoblastic leukemia (B-ALL). 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 patients, ages 12 years and older, with relapsed or refractory B-ALL
             who have failed, or are intolerant to, any established therapy; or for whom no other
             treatment options are available.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

          -  Serum/plasma creatinine ≤1.5mg/dL.

          -  Serum/plasma 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.

          -  White Blood Cell Count value of <15,000 cells/μL prior to Cycle 1 Day 1.

          -  Negative urine or serum beta-human chorionic gonadotropin (β-HCG) pregnancy test
             within 7 days prior to the Cycle 1, Day 1 visit, for women of childbearing potential.

          -  Males, and female patients who are biologically capable of having children, must agree
             to use a medically acceptable method of birth control.

        Exclusion Criteria:

          -  Patients who have an option for other treatment for B-ALL at the current state of
             disease.

          -  Known active central nervous system (CNS) leukemia.

          -  Patients with Burkitt's leukemia/lymphoma.

          -  Active graft-versus-host disease.

          -  Autologous or allogenic transplant within the 60 days prior to Screening.

          -  Known history of immunogenicity or hypersensitivity to a CD19 antibody.

          -  Known history of positive serum human ADA.

          -  Active autoimmune disease, motor neuropathy considered of autoimmune origin, or other
             central nervous system autoimmune disease.

          -  Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen
             (HbsAg), or antibody to hepatitis C virus (anti-HCV).

          -  History of Stevens-Johnson syndrome or toxic epidermal necrolysis syndrome.

          -  Pregnant or breastfeeding women.

          -  Significant medical comorbidities, including uncontrolled hypertension (diastolic
             blood pressure >115 mm Hg), unstable angina, congestive heart failure (greater than
             New York Heart Association class II), severe uncontrolled ventricular arrhythmias,
             electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe
             chronic pulmonary disease, coronary angioplasty, 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 <14 days prior to the start of treatment on Cycle 1, Day 1, except if approved by
             the Sponsor.

          -  Major surgery, chemotherapy, systemic therapy (excluding hydroxyurea,steroids and any
             targeted small molecules or biologics), or radiotherapy, within 14 days or 5
             half-lives (whichever is shorter) prior to the Cycle 1, Day 1 treatment, except if
             approved by the Sponsor.

          -  Failure to recover from acute non hematologic toxicity (except alopecia or Grade 2 or
             lower neuropathy), due to previous therapy, prior to Screening.

          -  Isolated extramedullary relapse.

          -  Congenital long QT syndrome or a corrected QTc interval of ≥450 ms at the Screening
             visit.

          -  Active second primary malignancy other than non-melanoma skin cancers, nonmetastatic
             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
             patient inappropriate for study participation or put the patient at risk.