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

NCT02588092 | Terminated Phase 1 Results

• 1 other identifier: ADCT-301-002
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 11

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.

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia

Keywords

Camidanlumab tesirine

Outcome Measures

Primary Outcomes (4)

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

  A DLT is defined as any of the following events, except those that are clearly due to underlying disease or extraneous causes: A hematologic DLT is defined as: \- Grade 3 or higher event of neutropenia or thrombocytopenia, or a Grade 4 anemia, with a hypocellular bone marrow lasting for 6 weeks or more after the start of a cycle, in the absence of residual leukemia (i.e., with \<5% blasts). In case of a normocellular bone marrow with \<5% blasts, 8 weeks with ≥Grade 3 pancytopenia will be considered a DLT. A non-hematologic DLT is defined as: * Grade 4 tumor lysis syndrome. * Grade 3 or higher AE (including nausea, vomiting, diarrhea, and electrolyte imbalances lasting more than 48 hours despite optimal therapy; excluding all grades of alopecia). * CTCAE Grade 3 or higher hypersensitivity reaction (regardless of premedication). * CTCAE Grade 3 or higher skin ulceration. * Peripheral sensory or motor neuropathy ≥ Grade 2.

  Day 1 to Day 21 (Cycle 1)

• Recommended Dose of ADCT-301 for Part 2

  The recommended dose was to be established by the dose escalation steering committee and based on safety findings during part 1 of the study.

  Day 1 to Day 21 (Cycle 1)

• Number of Participants Reporting One or More Treatment Emergent Adverse Events (TEAEs)

  A TEAE is defined as any adverse event not present before exposure to study drug or any event already present that worsens in either intensity or frequency after exposure to study drug.

  Day 1 to a maximum of 24 weeks (+ 30 days)

• Number of Participants Reporting One or More Treatment Emergent Serious Adverse Event (SAE)

  An SAE is defined as any event that results in death, is immediately life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. Hospitalization for elective procedures or for protocol compliance is not considered an SAE.

  Day 1 to a maximum of 24 weeks (+ 30 days)

Secondary Outcomes (27)

• Duration of Response (DOR)

  Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)

• Overall Response Rate (ORR)

  Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)

• Overall Survival (OS)

  Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)

• Number of Participants With Progression Free Survival (PFS)

  Screening, Day 19 visit (+/- 3 days) of Cycle 2 and each subsequent cycle up to 12 months after the last dose of study drug (1 cycle = 21 days)

• Maximum Observed Serum Concentration (Cmax) of ADCT-301 for the Q3W Dosing Schedule

  Before infusion, end of infusion, 1, 3, 6, 24, 48, and 96 hours after infusion, and on Days 8 and 19 of Cycle 1 and 2 (1 cycle = 21 days)

Study Arms (2)

Part 1: ADCT-301 (dose escalation)

EXPERIMENTAL

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.

Drug: ADCT-301

Part 2: ADCT-301 (dose expansion)

EXPERIMENTAL

Participants will be assigned to receive the recommended dose and/or schedule of ADCT-301 as determined by the Dose Escalation Steering Committee.

Drug: ADCT-301

Interventions

ADCT-301 DRUG

Intravenous infusion

Also known as: Camidanlumab tesirine

Part 1: ADCT-301 (dose escalation); Part 2: ADCT-301 (dose expansion)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• ADC Therapeutics S.A.: lead

Study Sites (11)

Winship Cancer Institute, Emory University

Atlanta, Georgia, 30322, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

The University of Chicago Medical Center

Chicago, Illinois, 60647, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

Greenville Health System, Institute for Translational Oncology Research

Greenville, South Carolina, 29605, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

University of Washington Medical Center

Seattle, Washington, 98109, United States

Location

Froedtert Hospital/ Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Goldberg AD, Atallah E, Rizzieri D, Walter RB, Chung KY, Spira A, Stock W, Tallman MS, Cruz HG, Boni J, Havenith KEG, Chao G, Feingold JM, Wuerthner J, Solh M. Camidanlumab tesirine, an antibody-drug conjugate, in relapsed/refractory CD25-positive acute myeloid leukemia or acute lymphoblastic leukemia: A phase I study. Leuk Res. 2020 Aug;95:106385. doi: 10.1016/j.leukres.2020.106385. Epub 2020 Jun 7.

  PMID: 32521310 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

Only a small number of participants were analyzed as the study was early terminated due to slow enrollment.

Results Point of Contact

• Title: ADC Therapeutics
• Organization: ADC Therapeutics

clinical.trials@adctherapeutics.com

954-903-7994

Study Officials

• Aaron Goldberg, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2015
• First Posted: October 27, 2015
• Study Start: February 1, 2016
• Primary Completion: August 29, 2018
• Study Completion: August 29, 2018
• Last Updated: February 26, 2020
• Results First Posted: February 26, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)