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Trial record 1 of 1 for:    NCT03684694
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Safety and Efficacy Study of Loncastuximab Tesirine + Ibrutinib in Diffuse Large B-Cell or Mantle Cell Lymphoma

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ClinicalTrials.gov Identifier: NCT03684694
Recruitment Status : Recruiting
First Posted : September 26, 2018
Last Update Posted : October 15, 2021
Sponsor:
Information provided by (Responsible Party):
ADC Therapeutics S.A.

Tracking Information
First Submitted Date  ICMJE September 11, 2018
First Posted Date  ICMJE September 26, 2018
Last Update Posted Date October 15, 2021
Actual Study Start Date  ICMJE December 1, 2018
Estimated Primary Completion Date April 15, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 26, 2021)
  • Phase 1: Number of Adverse Events (AEs) [ Time Frame: Up to 3.5 years ]
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment.
  • Phase 1: Number of Adverse Events (AEs) of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Up to 3.5 years ]
    Adverse events will be graded according to CTCAE v4.0 (or more recent):
    • Grade 3 - Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living (ADL).
    • Grade 4 - Life-threatening consequences; urgent intervention indicated.
    • Grade 5 - Death related to adverse event.
    For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5.
  • Phase 1: Number of Serious Adverse Events (SAEs) [ Time Frame: Up to 3.5 years ]
    A SAE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance is not considered an SAE), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgement may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above.
  • Phase 1: Number of Serious Adverse Events (SAEs) of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Up to 3.5 years ]
    Adverse events will be graded according to CTCAE v4.0 (or more recent):
    • Grade 3 - Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL.
    • Grade 4 - Life-threatening consequences; urgent intervention indicated.
    • Grade 5 - Death related to adverse event.
    For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5.
  • Phase 1: Number of Dose-Limiting Toxicities (DLTs) [ Time Frame: Up to 2 years ]
    Safety and Tolerability (dose escalation only).
  • Phase 1: Number of Dose Interruptions [ Time Frame: Up to 2 years ]
    Safety and Tolerability.
  • Phase 1: Number of Dose Reductions [ Time Frame: Up to 2 years ]
    To characterize the safety and tolerability of loncastuximab tesirine in combination with ibrutinib, and to identify the MTD/recommended dose and schedule for future studies.
  • Phase 1: Number of Participants who Experience a Clinically Significant Change in Baseline in Laboratory Values [ Time Frame: Up to 3.5 years ]
    To characterize the safety and tolerability of loncastuximab tesirine in combination with ibrutinib, and to identify the MTD/recommended dose and schedule for future studies.
  • Phase 1: Number of Participants who Experience a Clinically Significant Change in Baseline in Vital Signs [ Time Frame: Up to 3.5 years ]
    To characterize the safety and tolerability of loncastuximab tesirine in combination with ibrutinib, and to identify the MTD/recommended dose and schedule for future studies.
  • Phase 1: Number of Participants who Experience a Clinically Significant Change in Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Up to 3.5 years ]
    To characterize the safety and tolerability of loncastuximab tesirine in combination with ibrutinib, and to identify the MTD/recommended dose and schedule for future studies.
  • Phase 1: Number of Participants who Experience a Clinically Significant Change in Baseline in Electrocardiogram (ECG) Results [ Time Frame: Up to 3.5 years ]
    To characterize the safety and tolerability of loncastuximab tesirine in combination with ibrutinib, and to identify the MTD/recommended dose and schedule for future studies.
  • Phase 2: Complete Response Rate (CRR) [ Time Frame: Up to 2 years ]
    CRR according to the 2014 Lugano classifications determined by Independent Review Committee (IRC). CRR defined as the number of participants with a best overall response (BOR) of complete response (CR) in non-germinal center B-cell diffuse large B-cell lymphoma (non-GCB DLBCL) participant cohort only (Phase 2).
Original Primary Outcome Measures  ICMJE
 (submitted: September 24, 2018)
  • Safety and tolerability of loncastuximab tesirine in combination with ibrutinib by measuring frequency and severity of adverse events (AEs) [ Time Frame: Until 30 days after last dose ]
  • Safety and tolerability of loncastuximab tesirine in combination with ibrutinib by measuring frequency and severity of serious adverse events (SAEs) [ Time Frame: Until 30 days after last dose ]
  • Safety and tolerability of loncastuximab tesirine in combination with ibrutinib by measuring incidence of dose limiting toxicities (DLTs) (dose escalation only) [ Time Frame: First 21-day cycle for each patient (dose escalation only) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 24, 2020)
  • Phase 1: Overall Response Rate (ORR) [ Time Frame: Up to 2 years ]
    ORR according to the 2014 Lugano classification, defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR).
  • Phase 1 and Phase 2: Duration of Response (DOR) [ Time Frame: Up to 2 years ]
    DOR defined as the time from first tumor response to disease progression or death.
  • Phase 1 and Phase 2: Relapse-Free Survival (RFS) [ Time Frame: Up to 2 years ]
    Time from the documentation of complete response (CR) to disease progression or death.
  • Phase 1 and Phase 2: Progression-Free Survival (PFS) [ Time Frame: Up to 2 years ]
    Time between start of treatment and the first documentation of progression, or death.
  • Phase 1 and Phase 2: Overall survival (OS) [ Time Frame: Up to 2 years ]
    Time between the start of treatment and death from any cause.
  • Phase 1 and Phase 2: Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) [ Time Frame: Day 1 (pre-dose, end of infusion and 4 hours post-dose), Day 8 and Day 15 of Cycles 1 and 2 (Cycle length is 3 weeks) and Day 1 of Cycle 3 onwards (Cycle length is 4 weeks) ]
  • Phase 1 and Phase 2: Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) [ Time Frame: Day 1 (pre-dose, end of infusion and 4 hours post-dose), Day 8 and Day 15 of Cycles 1 and 2 (Cycle length is 3 weeks) and Day 1 of Cycle 3 onwards (Cycle length is 4 weeks) ]
  • Phase 1 and Phase 2: Area Under the Concentration-Time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) [ Time Frame: Day 1 (pre-dose, end of infusion and 4 hours post-dose), Day 8 and Day 15 of Cycles 1 and 2 (Cycle length is 3 weeks) and Day 1 of Cycle 3 onwards (Cycle length is 4 weeks) ]
  • Phase 1 and Phase 2: Area Under the Concentration-Time Curve from Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) [ Time Frame: Day 1 (pre-dose, end of infusion and 4 hours post-dose), Day 8 and Day 15 of Cycles 1 and 2 (Cycle length is 3 weeks) and Day 1 of Cycle 3 onwards (Cycle length is 4 weeks) ]
  • Phase 1 and Phase 2: Area Under the Concentration-Time Curve from Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) [ Time Frame: Day 1 (pre-dose, end of infusion and 4 hours post-dose), Day 8 and Day 15 of Cycles 1 and 2 (Cycle length is 3 weeks) and Day 1 of Cycle 3 onwards (Cycle length is 4 weeks) ]
  • Phase 1 and Phase 2: Clearance (CL) of Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) [ Time Frame: Day 1 (pre-dose, end of infusion and 4 hours post-dose), Day 8 and Day 15 of Cycles 1 and 2 (Cycle length is 3 weeks) and Day 1 of Cycle 3 onwards (Cycle length is 4 weeks) ]
  • Phase 1 and Phase 2: Accumulation Index (AI) Loncastuximab Tesirine (Total Antibody, PBD-Conjugated Antibody and Unconjugated Cytotoxin SG3199) [ Time Frame: Day 1 (pre-dose, end of infusion and 4 hours post-dose), Day 8 and Day 15 of Cycles 1 and 2 (Cycle length is 3 weeks) and Day 1 of Cycle 3 onwards (Cycle length is 4 weeks) ]
  • Phase 1 and Phase 2: Number of Participants with Anti-Drug Antibody (ADA) Titers to Loncastuximab Tesirine [ Time Frame: Day 1 and Day 15 of Cycle 1, Day 1 of Cycle 2 (Cycle length is 3 weeks) and Day 1 of Cycle 3 onwards (Cycle length is 4 weeks) ]
    Followed by characterization and evaluation of neutralizing capacity as needed.
  • Phase 2: Overall Response Rate (ORR) [ Time Frame: Up to 2 years ]
    ORR according to the 2014 Lugano classification, defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR).
  • Phase 2: Complete Response Rate (CRR) in GCB DLBCL, all DLBCL and MCL Participants [ Time Frame: Up to 2 years ]
    CRR according to the 2014 Lugano classifications determined by the investigator and/or independent review committee (IRC). CRR defined as the number of participants with a best overall response (BOR) of complete response (CR) in non-GCB DLBCL, GCB DLBCL, all DLBCL, and MCL participants.
  • Phase 2: Complete Response Rate (CRR) in Non-GCB DLBCL Participants [ Time Frame: Up to 2 years ]
    CRR according to the 2014 Lugano classifications determined by the investigator and/or independent review committee (IRC). CRR defined as the number of participants with a best overall response (BOR) of complete response (CR) in non-GCB DLBCL participants.
  • Phase 2: Number of Adverse Events (AEs) [ Time Frame: Up to 3.5 years ]
    An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product, which does not necessarily have to have a causal relationship with this treatment.
  • Phase 2: Number of Adverse Events (AEs) of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Up to 3.5 years ]
    AEs will be graded according to CTCAE v4.0 (or more recent).
    • Grade 3 - Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL.
    • Grade 4 - Life-threatening consequences; urgent intervention indicated.
    • Grade 5 - Death related to adverse event.
    For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5.
  • Phase 2: Number of Serious Adverse Events (SAEs) [ Time Frame: Up to 3.5 years ]
    A SAE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance is not considered an SAE), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgement may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above.
  • Phase 2: Number of Serious Adverse Events (SAEs) of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Up to 3.5 years ]
    Adverse events will be graded according to CTCAE v4.0 (or more recent):
    • Grade 3 - Severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL.
    • Grade 4 - Life-threatening consequences; urgent intervention indicated.
    • Grade 5 - Death related to adverse event.
    For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5.
  • Phase 2: Number of Participants who Experience a Clinically Significant Change in Baseline in Laboratory Values [ Time Frame: Up to 3.5 years ]
    To characterize the safety and tolerability of loncastuximab tesirine in combination with ibrutinib, and to identify the MTD/recommended dose and schedule for future studies.
  • Phase 2: Number of Participants who Experience a Clinically Significant Change in Baseline in Vital Signs [ Time Frame: Up to 3.5 years ]
    To characterize the safety and tolerability of loncastuximab tesirine in combination with ibrutinib, and to identify the MTD/recommended dose and schedule for future studies.
  • Phase 2: Phase 1: Number of Participants who Experience a Clinically Significant Change in Baseline in Eastern Cooperative Oncology Group (ECOG) [ Time Frame: Up to 3.5 years ]
    To characterize the safety and tolerability of loncastuximab tesirine in combination with ibrutinib, and to identify the MTD/recommended dose and schedule for future studies.
  • Phase 2: Number of Participants who Experience a Clinically Significant Change in Baseline in Electrocardiogram (ECG) Results [ Time Frame: Up to 3.5 years ]
    To characterize the safety and tolerability of loncastuximab tesirine in combination with ibrutinib, and to identify the MTD/recommended dose and schedule for future studies.
  • Phase 2: Functional Scales, Symptoms and Global Health State Scores as measured by The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 [ Time Frame: Baseline to End of Follow-Up Period (maximum time on follow-up was 2 years) ]
  • Phase 2: Lymphoma Subscale (LymS) of Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Scores [ Time Frame: Baseline to End of Follow-Up Period (maximum time on follow-up was 2 years) ]
  • Phase 2: EuroQoL 5-dimension 5-level (EQ-5D-5L) [ Time Frame: Baseline to End of Follow-Up Period (maximum time on follow-up was 2 years) ]
    Change from Baseline in Visual Analog Scale scores (VAS) at each scheduled assessment. Individual dimension responses will be summarized at each scheduled assessment with frequency counts and percentage of participants.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2018)
  • Overall response rate (ORR) [ Time Frame: Up to 2 years ]
    ORR according to the 2014 Lugano classification, defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR)
  • Complete Response Rate (CR) [ Time Frame: Up to 2 years ]
    CR rate defined as the percentage of treated patients with a BOR of CR
  • Duration of Response (DOR): time from first tumor response to disease progression or death [ Time Frame: Up to 2 years ]
  • Overall survival (time between the start of treatment and death from any cause) [ Time Frame: Up to 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of Loncastuximab Tesirine + Ibrutinib in Diffuse Large B-Cell or Mantle Cell Lymphoma
Official Title  ICMJE A Phase 1/2 Open-Label Study to Evaluate the Safety and Efficacy of Loncastuximab Tesirine and Ibrutinib in Patients With Advanced Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma (LOTIS-3)
Brief Summary The purpose of this Phase 1/2 study is to evaluate the safety and efficacy of Loncastuximab Tesirine (ADCT-402) in combination with Ibrutinib in participants with Advanced Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma.
Detailed Description

The Phase 1 portion of the study will cover the dose escalation portion of the study. This will then be followed by the Phase 2 portion of the study, which will treat participants with the dose of loncastuximab tesirine determined in the Phase 1 portion of the study. The ibrutinib dose of 560 mg daily, will remain the same throughout both phases of the study.

A standard 3+3 dose escalation design will be used for the Phase 1 portion of the study. The dose-limiting toxicity (DLT) period will be the 21 days following the first dose of ibrutinib. The dose escalation cohort will receive loncastuximab tesirine for 2 cycles with concurrent ibrutinib (concomitant therapy) and may then continue ibrutinib therapy up to one year.

The Phase 2 portion of the study will involve 3 cohorts:

  • Non-germinal center B-cell diffuse large B-cell lymphoma (Non-GCB DLBCL) cohort
  • Germinal center B-cell diffuse large B-cell lymphoma (GCB DLBCL) cohort
  • Mantle cell lymphoma (MCL) cohort

Each of the cohorts will be treated with the recommended dose of loncastuximab tesirine determined in the Phase 1 portion of the study.

The study will include a Screening Period (of up to 28 days), a Treatment Period (cycles of 3 to 4 weeks), and a Follow-up Period (approximately every 12 week visits for up to 2 years after treatment discontinuation).

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Diffuse Large B-Cell Lymphoma
  • Mantle Cell Lymphoma
Intervention  ICMJE
  • Drug: Loncastuximab Tesirine
    Intravenous (IV) infusion.
    Other Names:
    • Zynlonta
    • ADCT-402
  • Drug: Ibrutinib
    Oral capsule.
Study Arms  ICMJE
  • Experimental: Phase 1: Dose-Escalation of ADCT-402
    A standard 3+3 dose escalation design will be used. The dose-limiting toxicity (DLT) period will be the 21 days following the first dose of ibrutinib. The dose escalation cohort will receive loncastuximab tesirine for Cycle 1 and 2 (3 weeks each) with concurrent ibrutinib (concomitant therapy) daily. Participants may continue to receive treatment up to 1 year after Cycle 1 Day 1 (once every 4 weeks from Cycle 3 onwards). Loncastuximab tesirine will be administered intravenously (IV), as a frozen liquid.
    Interventions:
    • Drug: Loncastuximab Tesirine
    • Drug: Ibrutinib
  • Experimental: Phase 2: MTD or RP2D of ADCT-402 in Non-GCB DLBCL
    Participants with non-germinal center B-cell diffuse large B-cell lymphoma (Non-GCB DLBCL) will receive the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of loncastuximab tesirine, as determined in Phase 1, once every 3 weeks for Cycle 1 and 2 and a daily dose of ibrutinib. Participants can continue treatment up to 1 year (once every 4 weeks from Cycle 3 onwards). Loncastuximab tesirine will be administered intravenously (IV), as a lyophilized formulation.
    Interventions:
    • Drug: Loncastuximab Tesirine
    • Drug: Ibrutinib
  • Experimental: Phase 2: MTD or RP2D of ADCT-402 in GCB DLBCL
    Participants with germinal center B-cell diffuse large B-cell lymphoma (GCB DLBCL) will receive the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of loncastuximab tesirine, as determined in Phase 1, once every 3 weeks for Cycle 1 and 2 and a daily dose of ibrutinib. Participants can continue treatment up to 1 year (once every 4 weeks from Cycle 3 onwards). Loncastuximab tesirine will be administered intravenously (IV), as a lyophilized formulation.
    Interventions:
    • Drug: Loncastuximab Tesirine
    • Drug: Ibrutinib
  • Experimental: Phase 2: MTD or RP2D of ADCT-402 in MCL
    Participants with mantle cell lymphoma (MCL) will receive the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of loncastuximab tesirine, as determined in Phase 1, once every 3 weeks for Cycle 1 and 2 and a daily dose of ibrutinib. Participants can continue treatment up to 1 year (once every 4 weeks from Cycle 3 onwards). Loncastuximab tesirine will be administered intravenously (IV), as a lyophilized formulation.
    Interventions:
    • Drug: Loncastuximab Tesirine
    • Drug: Ibrutinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 24, 2020)
161
Original Estimated Enrollment  ICMJE
 (submitted: September 24, 2018)
60
Estimated Study Completion Date  ICMJE April 14, 2023
Estimated Primary Completion Date April 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Male or female participant aged 18 years or older
  2. Pathologic diagnosis of DLBCL or MCL (For Italy Sites Only: MCL patients are excluded.)
  3. Participants with DLBCL must have relapsed or refractory disease and have failed or been intolerant to available standard therapy
  4. Participants with MCL must have relapsed or refractory disease and have received at least one prior line of therapy (For Italy Sites Only: This exclusion criterion is not applicable)
  5. Participants who have received previous CD19-directed therapy must have a biopsy which shows CD19 expression after completion of the CD19-directed therapy
  6. Measurable disease as defined by the 2014 Lugano Classification
  7. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available)
  8. ECOG performance status 0 to 2
  9. Screening laboratory values within the following parameters:

    1. Absolute neutrophil count (ANC) ≥1.0 × 103/µL (off growth factors at least 72 hours)
    2. Platelet count ≥75 × 103/µL without transfusion in the past 7 days
    3. Hemoglobin ≥8 g/dL (4.96 mmol/L), transfusion allowed
    4. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤2.5 × the ULN
    5. Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × ULN)
    6. Blood creatinine ≤1.5 × ULN or calculated creatinine clearance ≥60 mL/min by the Cockcroft and Gault equation
  10. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days prior to start of study drugs on C1D1 for women of childbearing potential
  11. Women of childbearing potential must agree to use a highly effective method of contraception from the time of giving informed consent until at least 9 months after the last dose of loncastuximab tesirine or 1 month after last dose of ibrutinib, whichever comes last. Men with female partners who are of childbearing potential must agree that they will use a highly effective method of contraception from the time of giving informed consent until at least 6 months after the participant receives his last dose of loncastuximab tesirine or 3 months after last dose of ibrutinib, whichever comes last

Exclusion Criteria:

  1. Known history of hypersensitivity to or positive serum human anti-drug antibody (ADA) to a CD19 antibody
  2. Known history of hypersensitivity to ibrutinib
  3. Previous therapy with ibrutinib or other BTK inhibitors
  4. Previous therapy with loncastuximab tesirine
  5. Requires treatment or prophylaxis with a moderate or strong cytochrome P450 (CYP) 3A inhibitor
  6. Allogenic or autologous transplant within 60 days prior to start of study drugs (C1D1)
  7. Active graft-versus-host disease
  8. Post-transplantation lymphoproliferative disorder
  9. Active autoimmune disease, including motor neuropathy considered of autoimmune origin and other central nervous system (CNS) autoimmune disease
  10. Known seropositive and requiring anti-viral therapy for human immunodeficiency (HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV).
  11. History of Stevens-Johnson syndrome or toxic epidermal necrolysis
  12. Lymphoma with active CNS involvement at the time of screening, including leptomeningeal disease
  13. Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath)
  14. Breastfeeding or pregnant
  15. Significant medical comorbidities, including but not limited to, uncontrolled hypertension (blood pressure [BP] ≥160/100 millimeters of mercury (mmHg) repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes mellitus, or severe chronic pulmonary disease, or tuberculosis infection (tuberculosis screening based on local standards).
  16. Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drugs (C1D1), except shorter if approved by the Sponsor
  17. Use of any other experimental medication within 14 days prior to start of study drugs (C1D1)
  18. Planned live vaccine administration after starting study drugs (C1D1)
  19. Any condition that could interfere with the absorption or metabolism of ibrutinib including malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel
  20. Inherited or acquired bleeding disorders
  21. Ongoing anticoagulation treatment, except for low-dose heparinisation or equivalent
  22. Failure to recover to Grade ≤1 (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) from acute non-hematologic toxicity (Grade ≤2 neuropathy or alopecia) due to previous therapy prior to screening
  23. Congenital long QT syndrome or a corrected QTcF interval of >480 ms at screening (unless secondary to pacemaker or bundle branch block)
  24. Active second primary malignancy other than non-melanoma skin cancers, non metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in situ of the breast, or other malignancy that the Sponsor's medical monitor and Investigator agree, and document should not be exclusionary
  25. Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgement, make the participant inappropriate for study participation or put the participant at risk
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: ADC Therapeutics 954-903-7994 clinical.trials@adctherapeutics.com
Listed Location Countries  ICMJE Belgium,   France,   Italy,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03684694
Other Study ID Numbers  ICMJE ADCT-402-103
2018-002625-38 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party ADC Therapeutics S.A.
Study Sponsor  ICMJE ADC Therapeutics S.A.
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account ADC Therapeutics S.A.
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP