Study of ADCT-301 in Patients With Relapsed/Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia (ALL)

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Brief Title

Study of ADCT-301 in Patients With Relapsed/Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia (ALL)

Official Title

A Phase 1, Open-label, Dose-escalation, Multicenter Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Activity of ADCT 301 in Patients With Relapsed or Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia

Brief 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.
    

Detailed Description

      This is a Phase 1 study with ADCT-301 to evaluate the safety, tolerability and
      pharmacokinetics of ADCT-301 in participants with Acute Myeloid Leukemia (AML) or Acute
      Lymphoblastic Leukemia (ALL).

      ADCT-301 is a human monoclonal antibody attached via a cleavable linker to a
      pyrrolobenzodiazepine (PBD) warhead which, when internalized by antigen expressing cells,
      covalently cross links deoxyribonucleic acid (DNA) preventing replication.

      The study will be conducted in 2 parts: In Part 1 (dose escalation) participants will either
      be on weekly administration or every 3-week administration. Participants on weekly
      administration will receive an infusion of ADCT-301 on Days 1, 8, and 15 of each 3 week
      treatment cycle. Participants on 3-week administration will receive an infusion of ADCT-301
      on Day 1, every 3 weeks. Dose escalation will continue until the maximum tolerated dose (MTD)
      is determined.

      In Part 2 (expansion), participants will be assigned to receive a recommended dose and/or
      schedule of ADCT-301 as determined by a Dose Escalation Steering Committee.

      For each participant, the study will include a screening period (up to 28 days), a treatment
      period, and a follow-up period to assess disease progression and survival for up to 12 months
      after the last dose of study drug. The total study duration will be dependent on overall
      participant tolerability to the study drug and response to treatment. It is anticipated that
      the entire study (Parts 1 and 2) will enroll a maximum of 80 participants and could last
      approximately 3 years from first participant treated to last participant completed.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Number of Participants Who Experienced Dose-Limiting Toxicities (DLT)

Secondary Outcome

 Duration of Response (DOR)

Condition

Acute Myeloid Leukemia

Intervention

ADCT-301

Study Arms / Comparison Groups

 Part 1: ADCT-301 (dose escalation)
Description:  Weekly administration - Participants will receive an IV infusion of ADCT-301, on Days 1, 8, and 15 of each 3-week (21-day) cycle.
3-week administration - Participants will receive an IV infusion of ADCT-301, on Day 1 of each 3-week (21-day) cycle.
The dose escalation will be conducted according to a 3+3 design.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

35

Start Date

February 1, 2016

Completion Date

August 29, 2018

Primary Completion Date

August 29, 2018

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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Aaron Goldberg, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02588092

Organization ID

ADCT-301-002


Responsible Party

Sponsor

Study Sponsor

ADC Therapeutics S.A.


Study Sponsor

Aaron Goldberg, MD, Principal Investigator, Memorial Sloan Kettering Cancer Center


Verification Date

February 2020