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Trial record 2 of 2 for:    ADCT402

Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Acute Lymphoblastic Leukemia (B-ALL)

This study is currently recruiting participants.
Verified August 2017 by ADC Therapeutics S.A.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02669264
First Posted: February 1, 2016
Last Update Posted: August 7, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
ADC Therapeutics S.A.
  Purpose
This study evaluates ADCT-402 in patients with relapsed or refractory B-cell lineage acute lymphoblastic leukemia (B-ALL). Patients will participate in a dose-escalation phase (Part 1) and dose expansion (Part 2). In Part 2, patients will receive the dose level identified in Part 1.

Condition Intervention Phase
Acute Lymphoblastic Leukemia Drug: ADCT-402 Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1, Open-label, Adaptive Dose-escalation, Multicenter Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Anti-tumor Activity of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Acute Lymphoblastic Leukemia (B-ALL)

Resource links provided by NLM:


Further study details as provided by ADC Therapeutics S.A.:

Primary Outcome Measures:
  • Assessment of Dose Limiting Toxicities (DLT) and Determination of the Maximum Tolerated Dose (MTD) of ADCT-402. [ Time Frame: 21 day cycle ]

Secondary Outcome Measures:
  • Evaluate the clinical activity of ADCT-402 as measured by the patient's response to treatment (complete response [CR], CR with incomplete blood count recovery [CRi], partial response [PR], Progressive Disease (PD), or no response [NR]) [ Time Frame: Disease assessments will be conducted within 6 days prior to Day 1 of Cycle 3, 5, and at each subsequent cycle, until disease progression, CR, CRi, or PR, assessed up to 12 months after last dose of study drug ]
  • Evaluate the clinical activity of ADCT-402 as measured by overall response rate (ORR) [ Time Frame: Disease assessments will be conducted within 6 days prior to Day 1 of Cycle 3, 5, and at each subsequent cycle, until discontinuation, assessed up to 12 months after last dose of study drug ]
    The ORR will be defined as the proportion of patients with a best overall response of CR, CRi or PR at the time each patient discontinues treatment with ADCT-402.

  • Evaluate the clinical activity of ADCT-402 as measured by duration of response (DOR) [ Time Frame: Disease assessments will be conducted within 6 days prior to Day 1 of Cycle 3, 5, and at each subsequent cycle, until discontinuation, assessed up to 12 months after last dose of study drug ]
    Duration of response will be defined among responders (CR, CRi, PR) as the time from the earliest date of first response until the first date of either disease progression or death due to any cause.

  • Evaluate the clinical activity of ADCT-402 as measured by overall survival (OS) [ Time Frame: Time from the first dose of study drug treatment until the date of death due to any cause, assessed up to 12 months after last dose of study drug ]
  • Evaluate the clinical activity of ADCT-402 as measured by progression-free survival (PFS) [ Time Frame: Disease assessments will be conducted within 6 days prior to Day 1 of Cycle 3, 5, and at each subsequent cycle, until disease progression, assessed up to 12 months after last dose of study drug ]
    Progression-free survival will be defined as the time from first dose of study drug until the first date of either disease progression or death due to any cause.

  • Pharmacokinetic (PK) profile of ADCT-402 (total antibody; drug to-antibody ratio [DAR] ≥0), PBD-conjugated antibody (DAR ≥1), and free warhead SG3199. Analysis of Cmax [ Time Frame: Blood sample collection within each cycle based on dosing schedule, until disease progression/discontinuation, 30 days and 12 weeks after last dose ]
    Noncompartmental analysis of Cmax

  • Pharmacokinetic (PK) profile of ADCT-402 (total antibody; drug to-antibody ratio [DAR] ≥0), PBD-conjugated antibody (DAR ≥1), and free warhead SG3199. Analysis of Tmax [ Time Frame: Blood sample collection within each cycle based on dosing schedule, until disease progression/discontinuation, 30 days and 12 weeks after last dose ]
    Noncompartmental analysis of Tmax

  • Pharmacokinetic (PK) profile of ADCT-402 (total antibody; drug to-antibody ratio [DAR] ≥0), PBD-conjugated antibody (DAR ≥1), and free warhead SG3199. Analysis of AUC0 last [ Time Frame: Blood sample collection within each cycle based on dosing schedule, until disease progression/discontinuation, 30 days and 12 weeks after last dose ]
    Noncompartmental analysis of area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0 last)

  • Pharmacokinetic (PK) profile of ADCT-402 (total antibody; drug to-antibody ratio [DAR] ≥0), PBD-conjugated antibody (DAR ≥1), and free warhead SG3199. Analysis of AUC0-∞ [ Time Frame: Blood sample collection within each cycle based on dosing schedule, until disease progression/discontinuation, 30 days and 12 weeks after last dose ]
    Noncompartmental analysis of area under the concentration-time curve from time zero to infinity (AUC0-∞)

  • Pharmacokinetic (PK) profile of ADCT-402 (total antibody; drug to-antibody ratio [DAR] ≥0), PBD-conjugated antibody (DAR ≥1), and free warhead SG3199. Analysis of (AUC0-τ) [ Time Frame: Blood sample collection within each cycle based on dosing schedule, until disease progression/discontinuation, 30 days and 12 weeks after last dose ]
    Noncompartmental analysis of area under the concentration-time curve (AUC) from time zero to the end of the dosing interval (AUC0-τ)

  • Pharmacokinetic (PK) profile of ADCT-402 (total antibody; drug to-antibody ratio [DAR] ≥0), PBD-conjugated antibody (DAR ≥1), and free warhead SG3199. Analysis of AI [ Time Frame: Blood sample collection within each cycle based on dosing schedule, until disease progression/discontinuation, 30 days and 12 weeks after last dose ]
    Noncompartmental analysis of accumulation index (AI)

  • Pharmacokinetic (PK) profile of ADCT-402 (total antibody; drug to-antibody ratio [DAR] ≥0), PBD-conjugated antibody (DAR ≥1), and free warhead SG3199. Analysis of Vss [ Time Frame: Blood sample collection within each cycle based on dosing schedule, until disease progression/discontinuation, 30 days and 12 weeks after last dose ]
    Noncompartmental analysis of volume of distribution at a steady-state (Vss)

  • Pharmacokinetic (PK) profile of ADCT-402 (total antibody; drug to-antibody ratio [DAR] ≥0), PBD-conjugated antibody (DAR ≥1), and free warhead SG3199. Analysis of MRT [ Time Frame: Blood sample collection within each cycle based on dosing schedule, until disease progression/discontinuation, 30 days and 12 weeks after last dose ]
    Noncompartmental analysis of mean residence time (MRT)

  • Pharmacokinetic (PK) profile of ADCT-402 (total antibody; drug to-antibody ratio [DAR] ≥0), PBD-conjugated antibody (DAR ≥1), and free warhead SG3199. Analysis of λz [ Time Frame: Blood sample collection within each cycle based on dosing schedule, until disease progression/discontinuation, 30 days and 12 weeks after last dose ]
    Noncompartmental analysis of terminal elimination phase rate constant (λz)

  • Pharmacokinetic (PK) profile of ADCT-402 (total antibody; drug to-antibody ratio [DAR] ≥0), PBD-conjugated antibody (DAR ≥1), and free warhead SG3199. Analysis of T1/2 [ Time Frame: Blood sample collection within each cycle based on dosing schedule, until disease progression/discontinuation, 30 days and 12 weeks after last dose ]
    Noncompartmental analysis of terminal half-life (T1/2)

  • Pharmacokinetic (PK) profile of ADCT-402 (total antibody; drug to-antibody ratio [DAR] ≥0), PBD-conjugated antibody (DAR ≥1), and free warhead SG3199. Analysis of CL [ Time Frame: Blood sample collection within each cycle based on dosing schedule, until disease progression/discontinuation, 30 days and 12 weeks after last dose ]
    Noncompartmental analysis of clearance (CL)

  • Pharmacokinetic (PK) profile of ADCT-402 (total antibody; drug to-antibody ratio [DAR] ≥0), PBD-conjugated antibody (DAR ≥1), and free warhead SG3199. Analysis of Vz [ Time Frame: Blood sample collection within each cycle based on dosing schedule, until disease progression/discontinuation, 30 days and 12 weeks after last dose ]
    Noncompartmental analysis of volume of distribution (Vz)

  • Evaluate anti-drug antibodies (ADAs) in blood before, during, and after treatment with ADCT 402 [ Time Frame: Blood sample collection within each cycle based on dosing schedule, until disease progression/discontinuation, 30 days and 12 weeks after last dose ]
    Level of ADAs against ADCT-402 in serum.


Estimated Enrollment: 60
Study Start Date: March 2016
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ADCT-402

Weekly administration - Patients will receive an IV infusion of ADCT-402, on Days 1, 8, and 15 of each 3-week (21-day) cycle.

3-week administration - Patients will receive an IV infusion of ADCT-402, 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), all patients will be assigned to the recommended dose and/or schedule of ADCT-402 identified in Part 1 by the Dose Escalation Steering Committee.

Drug: ADCT-402
intravenous infusion

Detailed Description:

Study ADCT-402-102 is the first clinical study with ADCT-402 in patients with B-cell lineage acute lymphoblastic leukemia (ALL).

ADCT-402 is an antibody drug conjugate (ADC) composed of a humanized antibody directed against human cluster of differentiation 19 (CD19), stochastically conjugated via a valine-alanine cleavable, maleimide linker to a pyrrolobenzodiazepine (PBD) dimer cytotoxin.

The study will be conducted in 2 parts. In Part 1 (dose escalation) patients will receive an infusion of ADCT-402 either be on weekly administration or every 3-week administration. Patients on weekly administration will receive an infusion of ADCT-402 on Days 1, 8, and 15 of each 3 week treatment cycle. Patients on 3-week administration will receive an infusion of ADCT-402 on Day 1, every 3 weeks. Dose escalation will continue until the maximum tolerated dose (MTD) is determined.

In Part 2 (expansion), all patients will be assigned to the recommended dose and/or schedule of ADCT-402 identified in Part 1 by the Dose Escalation Steering Committee.

For each patient, the study will include a screening period (up to 28 days), a treatment period (until withdrawal), 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 duration of the entire study (Parts 1 and 2) could be approximately 3 years from first patient treated to last patient completed.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02669264


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

Locations
United States, California
UC San Diego Moores Cancer Center Recruiting
La Jolla, California, United States, 92093
Principal Investigator: Matthew Wieduwilt, MD, PhD         
United States, Connecticut
Smilow Cancer Hospital at Yale-New Haven Recruiting
New Haven, Connecticut, United States, 06510
Principal Investigator: Amer Zeidan, MBBS, MhS         
United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Principal Investigator: Leonard Heffner, Jr., MD         
United States, Illinois
The University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
Principal Investigator: Wendy Stock, MD         
United States, New Jersey
John Theurer Cancer Center at Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Principal Investigator: James McCloskey, MD         
Rutgers Cancer Institute of New Jersey Completed
New Brunswick, New Jersey, United States, 08903
United States, Ohio
University Hospital of Cleveland Recruiting
Cleveland, Ohio, United States, 44106
Principal Investigator: Benjamin Tomlinson, MD         
The Ohio State University Wexner Medical Center, James Cancer Hospital Recruiting
Columbus, Ohio, United States, 43210
Principal Investigator: Bhavana Bhatnagar, MD         
United States, Pennsylvania
Penn State Milton S. Hershey Medical Center Recruiting
Hershey, Pennsylvania, United States, 17033
Principal Investigator: Hong Zheng, MD         
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Nitin Jain, MD         
United States, Wisconsin
Froedtert Hospital & the Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Principal Investigator: Ehab Atallah, MD         
Sponsors and Collaborators
ADC Therapeutics S.A.
  More Information

Responsible Party: ADC Therapeutics S.A.
ClinicalTrials.gov Identifier: NCT02669264     History of Changes
Other Study ID Numbers: ADCT-402-102
First Submitted: January 21, 2016
First Posted: February 1, 2016
Last Update Posted: August 7, 2017
Last Verified: August 2017

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