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Trial record 1 of 1 for:    NCT02588092
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Study of ADCT-301 in Patients With Relapsed/Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia (ALL)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by ADC Therapeutics SARL
Sponsor:
Information provided by (Responsible Party):
ADC Therapeutics SARL
ClinicalTrials.gov Identifier:
NCT02588092
First received: August 13, 2015
Last updated: November 25, 2016
Last verified: November 2016
  Purpose

This study evaluates ADCT-301 in patients with Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL). Patients will participate in a dose-escalation phase (Part 1) and receive ADCT-301 every 3 weeks.

In Part 2 of the study, patients will receive a recommended dose of ADCT-301 every 3 weeks.


Condition Intervention Phase
Acute Myeloid Leukemia
Acute Lymphoblastic Leukemia
Drug: ADCT-301
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by ADC Therapeutics SARL:

Primary Outcome Measures:
  • Assessment of Dose Limiting Toxicities (DLT) and Determination of the Maximum Tolerated Dose [ Time Frame: The protocol-defined assessment period is 1 21-day cycle ]
    Dose Limiting toxicities as defined per protocol, as related to ADCT-301

  • Recommended dose of ADCT-301 for Part 2 [ Time Frame: Dose escalation according to 3+3 design. Dose increase to next higher level until determination of Maximum Tolerated Dose (MTD) or highest protocol allowed dose. Anticipated overall study duration (Parts 1 and 2) is 3 years. ]
    The Dose Escalation Steering Committee will recommend dose for the expansion phase based on assessment of safety findings and determinations of Dose Limiting Toxicities.


Secondary Outcome Measures:
  • Duration of Response (DOR) [ Time Frame: Disease progression evaluation will occur at each 21-day cycle and for up to 12 months after the last dose of study drug. ]
    DOR will be defined among responders as the time from the earliest date of first response until the first date of either disease progression or death.

  • Overall Response Rate (ORR) [ Time Frame: Disease progression evaluation will occur at each 21-day cycle and for up to 12 months after the last dose of study drug. ]
    ORR is defined as the proportion of patients with a best overall response of Complete Response (CR), Complete Response with incomplete blood count recovery (CRi), Partial Response (PR) or No Response (NR).

  • Overall Survival (OS) [ Time Frame: Disease progression evaluation will occur at each 21-day cycle and for up to 12 months after the last dose of study drug. ]
    OS is defined as the time from the first dose of study drug treatment until the date of death due to any cause.

  • Progression Free Survival (PFS) [ Time Frame: Disease progression evaluation will occur at each 21-day cycle and for up to 12 months after the last dose of study drug. ]
    PFS is defined as the time from first dose of study drug until the first date of either disease progression or death due to any cause.

  • Maximum concentration (Cmax) of ADCT-301, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 [ Time Frame: Blood samples on Day 1, 8 and 19 of cycles 1 and 2, on day 1 of cycle 3 and 12 weeks (+/- 1 week) after the last dose of study drug. ]
    Noncompartmental analysis of the maximum concentration (Cmax)

  • Time to maximum concentration (Tmax) of ADCT-301, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 [ Time Frame: Blood samples on Day 1, 8 and 19 of cycles 1 and 2, on day 1 of cycle 3 and 12 weeks (+/- 1 week) after the last dose of study drug. ]
    Noncompartmental analysis of the time to maximum concentration (Tmax)

  • Area under the curve (AUC0-last) of ADCT-301, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 [ Time Frame: Blood samples on Day 1, 8 and 19 of cycles 1 and 2, on day 1 of cycle 3 and 12 weeks (+/- 1 week) after the last dose of study drug. ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0-last)

  • Area under the curve (AUC0-τ) of ADCT-301, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 [ Time Frame: Blood samples on Day 1, 8 and 19 of cycles 1 and 2, on day 1 of cycle 3 and 12 weeks (+/- 1 week) after the last dose of study drug. ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to the end of the dosing interval (AUC0-τ)

  • Area under the curve (AUC0-∞) of ADCT-301, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 [ Time Frame: Blood samples on Day 1, 8 and 19 of cycles 1 and 2, on day 1 of cycle 3 and 12 weeks (+/- 1 week) after the last dose of study drug. ]
    Noncompartmental analysis of the area under the concentration-time curve from time zero to infinity (AUC0-∞)

  • Accumulation index (AI) of ADCT-301, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 [ Time Frame: Blood samples on Day 1, 8 and 19 of cycles 1 and 2, on day 1 of cycle 3 and 12 weeks (+/- 1 week) after the last dose of study drug. ]
    Noncompartmental analysis of the accumulation index (AI)

  • Volume of distribution at steady-state (Vss) of ADCT-301, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 [ Time Frame: Blood samples on Day 1, 8 and 19 of cycles 1 and 2, on day 1 of cycle 3 and 12 weeks (+/- 1 week) after the last dose of study drug. ]
    Noncompartmental analysis of the volume of distribution at steady-state (Vss)

  • Mean residence time (MRT) of ADCT-301, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 [ Time Frame: Blood samples on Day 1, 8 and 19 of cycles 1 and 2, on day 1 of cycle 3 and 12 weeks (+/- 1 week) after the last dose of study drug. ]
    Noncompartmental analysis of the mean residence time (MRT)

  • Terminal elimination phase rate constant (λz) of ADCT-301, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 [ Time Frame: Blood samples on Day 1, 8 and 19 of cycles 1 and 2, on day 1 of cycle 3 and 12 weeks (+/- 1 week) after the last dose of study drug. ]
    Noncompartmental analysis of the terminal elimination phase rate constant (λz)

  • Elimination half-life (T1/2) of ADCT-301, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 [ Time Frame: Blood samples on Day 1, 8 and 19 of cycles 1 and 2, on day 1 of cycle 3 and 12 weeks (+/- 1 week) after the last dose of study drug. ]
    Noncompartmental analysis of T1/2

  • Clearance (CL) of ADCT-301, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 [ Time Frame: Blood samples on Day 1, 7 and 19 of cycles 1 and 2, on day 1 of cycle 3 and 12 weeks (+/- 1 week) after the last dose of study drug. ]
    Noncompartmental analysis of clearance (CL)

  • Vz of ADCT-301, pyrrolobenzodiazepine (PBD) conjugated and warhead SG3199 [ Time Frame: Blood samples on Day 1, 8 and 19 of cycles 1 and 2, on day 1 of cycle 3 and 12 weeks (+/- 1 week) after the last dose of study drug. ]
    Noncompartmental analysis of Vz

  • Measurement of Anti-drug antibodies to ADCT-301 [ Time Frame: Blood samples on Day 1 of each cycle and 12 weeks (+/- 1 week) after the last dose of study drug. ]
    Measurement of Anti-drug antibodies to ADCT-301 before, during and after treatment with ADCT-301


Estimated Enrollment: 60
Study Start Date: December 2015
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ADCT-301

In Part 1 (dose-escalation), patients 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.

In Part 2 (expansion), patients will be assigned to receive the recommended dose of ADCT-301 as determined by the Dose Escalation Steering Committee (DESC).

Drug: ADCT-301
intravenous infusion

Detailed Description:

This is a Phase 1 study with ADCT-301 to evaluate the safety, tolerability and pharmacokinetics of ADCT-301 in patients 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) patients 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), patients will be assigned to receive a recommended dose of ADCT-301 as determined by a Dose Escalation Steering Committee.

For each patient, 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 patient 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 60 patients and could last approximately 3 years from first patient treated to last patient completed.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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 bilirubin ≤1.5 times the upper limit of normal (ULN).
  • 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.

Exclusion Criteria:

  • Patients 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 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 21 days prior to the Day 1 visit, 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02588092

Contacts
Contact: Maria Cincotta Maria.Cincotta@adctherapeutics.com
Contact: Jay Feingold Jay.Feingold@adctherapeutics.com

Locations
United States, Georgia
Northside Hospital Recruiting
Atlanta, Georgia, United States, 30342
Principal Investigator: Melhem Solh, MD         
United States, Illinois
The University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60647
Principal Investigator: Wendy Stock, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States
Principal Investigator: Martin Tallman, MD         
United States, North Carolina
Duke Cancer Center Recruiting
Durham, North Carolina, United States, 27710
Principal Investigator: David Rizzieri, MD         
United States, South Carolina
Greenville Health System, Institute for Translational Oncology Research Recruiting
Greenville, South Carolina, United States, 29605
Principal Investigator: Ki Y. Chung, MD         
United States, Texas
The University of Texas M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Nitin Jain, MD         
United States, Virginia
Virginia Cancer Specialists, PC Recruiting
Fairfax, Virginia, United States, 22031
Principal Investigator: Alexander Spira, MD         
United States, Washington
Swedish Cancer Institute Recruiting
Seattle, Washington, United States, 98104
Principal Investigator: Raya Mawad, MD         
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98109
Principal Investigator: Roland Walter, MD, Ph.D         
United States, Wisconsin
Froedtert Hospital/ Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Principal Investigator: Ehab Atallah, MD         
Sponsors and Collaborators
ADC Therapeutics SARL
  More Information

Responsible Party: ADC Therapeutics SARL
ClinicalTrials.gov Identifier: NCT02588092     History of Changes
Other Study ID Numbers: ADCT-301-002
Study First Received: August 13, 2015
Last Updated: November 25, 2016

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on March 29, 2017