Study of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL)
A Phase 1 Dose-escalation Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Antitumor Activity of ADCT-402 in Patients With Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL)
2 other identifiers
interventional
183
3 countries
11
Brief Summary
This study evaluates ADCT-402 in participants with Relapsed or Refractory B-cell Lineage Non Hodgkin Lymphoma (B-NHL). Participants will participate in a dose escalation phase (Part 1) and dose expansion (Part 2). In Part 2, participants will receive the dose level identified in Part 1.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2016
Typical duration for phase_1
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 21, 2016
CompletedFirst Posted
Study publicly available on registry
January 29, 2016
CompletedStudy Start
First participant enrolled
March 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 21, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
February 21, 2019
CompletedResults Posted
Study results publicly available
April 13, 2020
CompletedMay 19, 2021
April 1, 2021
3 years
January 21, 2016
February 19, 2020
April 27, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (4)
Number of Participants Who Experienced Dose-Limiting Toxicities (DLTs)
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: * CTCAE Grade 3 or 4 febrile neutropenia or neutropenic infection. * CTCAE Grade 4 neutropenia lasting \>7 days. * CTCAE Grade 4 thrombocytopenia. * CTCAE Grade 3 thrombocytopenia with clinically significant bleeding, or Grade 3 thrombocytopenia requiring a platelet transfusion. * CTCAE Grade 4 anemia. A non-hematologic DLT is defined as: * CTCAE Grade 4 tumor lysis syndrome (TLS). Grade 3 TLS will not constitute DLT unless it leads to irreversible end-organ damage. * CTCAE 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 2 or higher skin ulceration.
Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)
Recommended Dose of ADCT-402 for Part 2
The recommended dose was established by the dose escalation steering committee and based on safety findings during Part 1 of the study.
Q3W schedule: Day 1 to End of Cycle 1 (3 weeks); Q6W schedule: Day 1 to End of Cycle 1 (6 weeks)
Number of Participants Reporting at Least One Treatment Emergent Adverse Event (TEAE)
An adverse event (AE) is defined as any untoward medical occurrence in a participants enrolled into this study regardless of its causal relationship to study drug. A TEAE is defined as any 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 End of Study (a maximum of 18 months)
Number of Participants Reporting at Least One Treatment Emergent Serious Adverse Event (SAE)
An adverse event (AE) is defined as any untoward medical occurrence in a participant enrolled into this study regardless of its causal relationship to study drug. A treatment emergent AE (TEAE) is defined as any 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. 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.
Day 1 to End of Study (a maximum of 18 months)
Secondary Outcomes (14)
Overall Response Rate (ORR)
Baseline to End of Study (a maximum of 18 months)
Duration of Response (DoR)
Baseline to End of Study (a maximum of 18 months)
Overall Survival (OS)
Baseline to End of Study (a maximum of 18 months)
Progression-free Survival (PFS)
Baseline to End of Study (a maximum of 18 months)
Maximum Observed Serum Concentration (Cmax) for ADCT-402
Q3W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (3 weeks cycle); Q6W schedule: Day 1 (pre-dose and 1 to 6 hours post-dose), and days 2, 3, 5, 8, 15 and 21 of Cycles 1 and 2 (6 week cycle)
- +9 more secondary outcomes
Study Arms (2)
Part 1: ADCT-402 dose escalation
EXPERIMENTALIn Part 1 (dose escalation) participants will receive intravenous (IV) infusions of ADCT-402 at escalating doses, according to a 3+3 study design. Doses will be escalated from 15 µg/kg to 200 µg/kg on Day 1 of each cycle, with cycle lengths of 3 or 6 weeks.
Part 2: ADCT-402 dose expansion
EXPERIMENTALIn Part 2 (expansion), participants will be assigned to the recommended dose level(s) and schedule(s) of ADCT-402 identified in Part 1 by the Dose Escalation Steering Committee. Participants will receive intravenous (IV) infusions of ADCT-402 at either 120 μg/kg or 150 μg/kg on Day 1 of each 3 week cycle (Q3W).
Interventions
intravenous infusion
Eligibility Criteria
You may qualify if:
- Male or female participants, ages 18 years or older with pathologically confirmed relapsed or refractory B-cell lineage NHL who have failed or are intolerant to established therapy, or for whom no other treatment options are available.
- Refractory or relapsed B-cell NHL (per World health Organization \[WHO\] Classification system).
- Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block.
- Measurable disease, as defined by the 2014 Lugano Classification.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.
- Absolute neutrophil count (ANC) ≥1000/μL.
- Platelet count of ≥75000/μL.
- Hemoglobin ≥9.0 g/dL without transfusion within the 2 weeks prior to Day 1.
- Serum/plasma creatinine ≤1.5 mg/dL.
- Serum/plasma alkaline phosphatase, 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.
- Negative blood or urine beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to Day 1 for women of childbearing potential.
- Males, and female participants who are biologically capable of having children, must agree to use a medically acceptable method of birth control.
You may not qualify if:
- Participants who have any option for other treatment for B-cell NHL at the current state of disease.
- Active graft-versus-host disease.
- Autologous or allogenic transplant within the 60 days prior to the Screening visit.
- Known history of immunogenicity or hypersensitivity to a CD19 antibody.
- Evidence of myelodysplasia or myeloid leukemia by morphology, immunostains, flow cytometry, or cytogenetics on a bone marrow aspirate or biopsy.
- Known history of positive serum human ADA.
- Active autoimmune disease, motor neuropathy considered of autoimmune origin, and other central nervous system (CNS) autoimmune disease.
- Known seropositive for human immunodeficiency (HIV) virus, hepatitis B surface antigen (HbsAg), or antibody to hepatitis C virus (anti-HCV).
- History of Steven's Johnson's syndrome or toxic epidermal necrolysis syndrome.
- Pregnant or breastfeeding women.
- Significant medical comorbidities, including uncontrolled hypertension (diastolic blood pressure greater than 115 mm Hg), unstable angina, congestive heart failure (greater than New York Heart Association class II), severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia, poorly controlled diabetes, severe chronic pulmonary disease, coronary angioplasty, or 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 less than 14 days prior to start of study treatment on Cycle 1, Day 1, except if approved by Sponsor.
- Steroid use equivalent to greater than 20 mg of prednisone within 4 weeks (28 days) prior to Day 1.
- Major surgery, chemotherapy, systemic therapy (excluding steroids hydroxyurea steroids, and any targeted small molecules or biologics), or radiotherapy, 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 Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 0 or Grade 1) from acute non hematologic toxicity (except all grades alopecia or Grade 2 or lower neuropathy), due to previous therapy, prior to Screening.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
UC San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322, United States
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, 30342, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Columbia University Medical Center Herbert Irving Pavilion
New York, New York, 10032, United States
University Hospitals of Cleveland
Cleveland, Ohio, 44106, United States
Greenville Health System, Institute for Translational Oncology Research, Clinical Research Unit
Greenville, South Carolina, 29605, United States
Froedtert Hospital & the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
U.O Oncologia e Ematologia - Istituto Clinico Humanitas
Milan, Italy
University College London Hospitals
London, NW1 2BU, United Kingdom
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
Related Publications (3)
Hess B, Townsend W, Ai W, Stathis A, Solh M, Alderuccio JP, Ungar D, Liao S, Liao L, Khouri L, Zhang X, Boni J. Efficacy and Safety Exposure-Response Analysis of Loncastuximab Tesirine in Patients with B cell non-Hodgkin Lymphoma. AAPS J. 2021 Dec 10;24(1):11. doi: 10.1208/s12248-021-00660-3.
PMID: 34893942DERIVEDHamadani M, Radford J, Carlo-Stella C, Caimi PF, Reid E, O'Connor OA, Feingold JM, Ardeshna KM, Townsend W, Solh M, Heffner LT, Ungar D, Wang L, Boni J, Havenith K, Qin Y, Kahl BS. Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Blood. 2021 May 13;137(19):2634-2645. doi: 10.1182/blood.2020007512.
PMID: 33211842DERIVEDKahl BS, Hamadani M, Radford J, Carlo-Stella C, Caimi P, Reid E, Feingold JM, Ardeshna KM, Solh M, Heffner LT, Ungar D, He S, Boni J, Havenith K, O'Connor OA. A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Clin Cancer Res. 2019 Dec 1;25(23):6986-6994. doi: 10.1158/1078-0432.CCR-19-0711. Epub 2019 Nov 4.
PMID: 31685491DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- ADC Therapeutics
- Organization
- ADC Therapeutics
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
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
January 21, 2016
First Posted
January 29, 2016
Study Start
March 1, 2016
Primary Completion
February 21, 2019
Study Completion
February 21, 2019
Last Updated
May 19, 2021
Results First Posted
April 13, 2020
Record last verified: 2021-04
Data Sharing
- IPD Sharing
- Will not share