Study of ADCT-301 in Patients With Relapsed/Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia (ALL)
Condition: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: ADCT-301
Intervention description: Intravenous infusion
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: 18 Years
Healthy volunteers: No
Keywords: Camidanlumab tesirine

Summary:

      This study evaluates ADCT-301 in participants with Acute Myeloid Leukemia (AML) or Acute
      Lymphoblastic Leukemia (ALL). Participants will participate in a dose-escalation phase (Part
      1) and receive ADCT-301 either weekly or once every 3 weeks.

      In Part 2 of the study, participants will receive a recommended dose of ADCT-301 as
      determined by a Dose Escalation Steering Committee.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Relapsed or refractory CD25-positive AML [per World Health Organization (WHO)].

          -  Relapsed or refractory CD25-positive ALL [per World Health Organization (WHO)].

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2.

          -  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 the upper limit of normal.

          -  Women of childbearing potential must have a negative urine or serum beta-human
             chorionic gonadotropin pregnancy test within 7 days prior to Day 1.

          -  Women of childbearing potential must agree to use a highly effective method of
             contraception. Men with female partners who are of childbearing potential must agree
             that they or their partners will use a highly effective method of contraception.

          -  White Blood Cell Count value of <15,000 cells/μL prior to Cycle 1 Day 1.

        Exclusion Criteria:

          -  Participants who have an option for any treatment with proven clinical benefit for
             CD25-positive AML or CD25-positive ALL at current state of disease.

          -  Known active central nervous system (CNS) leukemia, defined as morphologic evidence of
             leukemic blasts in the cerebrospinal fluid (CSF), use of CNS directed intrathecal
             treatment for active disease within 28 days prior to Screening, or symptomatic CNS
             leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction)
             within 28 days prior to Screening.

          -  Active graft versus host disease.

          -  Autologous or allogenic transplant within the 60 days prior to Screening.

          -  Known history of immunogenicity or hypersensitivity to a CD25 antibody.

          -  Known history of positive serum human anti-drug antibodies (ADA), or known allergy to
             any component of ADCT-301.

          -  Active autoimmune disease; other CNS autoimmune disease. Known seropositive for human
             immunodeficiency (HIV) virus, hepatitis B surface antigen (HbsAg), or antibody to
             hepatitis C virus (anti-HCV) with confirmatory testing and requiring anti-viral
             therapy.

          -  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 the study treatment on Cycle 1, Day 1.

          -  Major surgery, chemotherapy, systemic therapy (excluding hydroxyurea, steroids, and
             any targeted small molecules or biologics), or radiotherapy, or biotherapy targeted
             therapies 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 CTCAE Version 4.0 Grade 0 or Grade 1) from acute non
             hematologic toxicity (except all grades of alopecia or Grade 2 or lower neuropathy),
             due to previous therapy, prior to Screening.

          -  Isolated extramedullary relapse (i.e., testicular, CNS).

          -  Congenital long QT syndrome or a corrected QT interval (QTc) ≥450 ms at Screening
             (unless secondary to pacemaker or bundle branch block).

          -  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.

          -  Any other significant medical illness, abnormality, or condition.