Safety and Efficacy Study of Loncastuximab Tesirine + Ibrutinib in Diffuse Large B-Cell or Mantle Cell Lymphoma

• ClinicalTrials.gov Identifier: NCT03684694
• Recruitment Status: Terminated
• First Posted: September 26, 2018
• Last Update Posted: February 1, 2023
• Sponsor: ADC Therapeutics S.A.
• Information provided by (Responsible Party): ADC Therapeutics S.A.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Diffuse Large B-Cell Lymphoma; Mantle Cell Lymphoma	Drug: Loncastuximab Tesirine; Drug: Ibrutinib	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 136 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: December 1, 2018
• Actual Primary Completion Date: November 18, 2022
• Actual Study Completion Date: November 18, 2022

Arms and Interventions

Arm	Intervention/treatment
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.	Drug: Loncastuximab Tesirine; Intravenous (IV) infusion.; Other Names: Zynlonta; ADCT-402; Drug: Ibrutinib; Oral capsule.
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.	Drug: Loncastuximab Tesirine; Intravenous (IV) infusion.; Other Names: Zynlonta; ADCT-402; Drug: Ibrutinib; Oral capsule.
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.	Drug: Loncastuximab Tesirine; Intravenous (IV) infusion.; Other Names: Zynlonta; ADCT-402; Drug: Ibrutinib; Oral capsule.
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.	Drug: Loncastuximab Tesirine; Intravenous (IV) infusion.; Other Names: Zynlonta; ADCT-402; Drug: Ibrutinib; Oral capsule.

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.

3. 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.
4. 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.

5. Phase 1: Number of Dose-Limiting Toxicities (DLTs) [ Time Frame: Up to 2 years ]
   Safety and Tolerability (dose escalation only).
6. Phase 1: Number of Dose Interruptions [ Time Frame: Up to 2 years ]
   Safety and Tolerability.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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).

Secondary Outcome Measures :

1. 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).
2. 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.
3. 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.
4. 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.
5. 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.
6. 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) ]
7. 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) ]
8. 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) ]
9. 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) ]
10. 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) ]
11. 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) ]
12. 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) ]
13. 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.
14. 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).
15. 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.
16. 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.
17. 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.
18. 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.

19. 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.
20. 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.

21. 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.
22. 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.
23. 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.
24. 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.
25. 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) ]
26. 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) ]
27. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

University of California Irvine Health Chao Family Comprehensive Cancer Center

Orange, California, United States, 92868

Redlands Community Hospital

Redlands, California, United States, 92373

United States, Florida

University of Miami

Miami, Florida, United States, 33136

Miami Cancer Institute

Miami, Florida, United States, 33176

United States, Georgia

The Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, United States, 30342

Georgia Cancer Center at Augusta University

Augusta, Georgia, United States, 30912

United States, Kentucky

Norton Cancer Institute, St. Matthews Campus

Louisville, Kentucky, United States, 40207

United States, Maryland

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States, 21287

United States, Michigan

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States, 48109

United States, Minnesota

University of Minnesota

Minneapolis, Minnesota, United States, 55455

United States, Montana

Saint Vincent Healthcare

Billings, Montana, United States, 59101

United States, Ohio

Case Western Reserve University

Cleveland, Ohio, United States, 44106

Belgium

GasthuisZusters Antwerpen Sint-Augustinus

Wilrijk, Belgium, 2610

CHU UCL Namur (Site Godinne)

Yvoir, Belgium, 5530

France

Centre Hospitalier Universitaire de Rennes Hôpital Pontchailou

Bretagne, France, 35033

Hôpital Hôtel-Dieu

Loiré, France, 44093

Hôpital Saint-Eloi

Montpellier, France, 34295

Hôpital Saint-Louis

Paris, France, 75475

Centre Hospitalier Lyon Sud

Pierre-Bénite, France, 69495

Centre Hospitalier Universitaire De Poitier - Hopital De La Miletrie - Hopital Jean Bernard

Poitiers, France, 86021

Italy

IRCCS istituto Clinico Humanitas U.O. di Oncologia ed Ematologia

Via Manzoni, Rozzano, Italy, 20089

Azienda Ospedaliera Pap Giovanni XXIII

Bergamo, Italy, 24127

Policlinico Sant'Orsola Malpighi

Bologna, Italy, 40138

Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia

Brescia, Italy, 25123

Istituto Scientifico Rmagnolo per lo Studio e la Cura dei Tumori

Meldola FC, Italy, 47014

Istituto Europeo di Oncologia

Milano, Italy, 20141

Azienda Unita Sanitaria Locale de Ravenna

Ravenna, Italy, 48100

Spain

Hospital Universitario Vall d'Hebrón

Barcelona, Spain, 08035

Hospital Duran I Reynals

Barcelona, Spain, 08908

Hospital General Universitario Gregorio Marañón

Madrid, Spain, 28007

Hospital Universitario Fundación Jiménez Díaz

Madrid, Spain, 28040

Hospital Universitario Marqués de Valdecilla

Santander, Spain, 39008

Hospital Universitario Virgen del Rocio

Sevilla, Spain, 41013

United Kingdom

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20 4BX

Abertawe Bro Morgannwg University Health Board

Swansea, United Kingdom, SA2 8QA

Sponsors and Collaborators

ADC Therapeutics S.A.

More Information

• Responsible Party: ADC Therapeutics S.A.
• ClinicalTrials.gov Identifier: NCT03684694
• Other Study ID Numbers: ADCT-402-103; 2018-002625-38 ( EudraCT Number )
• First Posted: September 26, 2018
• Last Update Posted: February 1, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ADC Therapeutics S.A.:

Loncastuximab Tesirine in Combination with Ibrutinib

Additional relevant MeSH terms:

Lymphoma; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Loncastuximab tesirine; Antineoplastic Agents, Immunological; Antineoplastic Agents