- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05144009
A Study of Loncastuximab Tesirine and Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Participants With Diffuse Large B-cell Lymphoma (DLBCL) (LOTIS-9)
A Phase 2 Open-label Study of Loncastuximab Tesirine in Combination With Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Patients With Diffuse Large B-cell Lymphoma (DLBCL) (LOTIS-9)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The primary objectives of this trial are shown below:
Cohort A: To assess the efficacy of a response-adapted treatment of Lonca-R in unfit participants with previously untreated DLBCL, high-grade B cell lymphoma (HGBCL), or Grade 3b follicular lymphoma (FL).
Cohort B: To assess the tolerability and efficacy of a response-adapted treatment of Lonca-R in frail participants with previously untreated DLBCL, or HGBCL, or Grade 3b FL who are ineligible for standard R-mini-CHOP.
The simplified geriatric assessment (sGA) developed by the Fondazione Italiana Linfomi (FIL) identifies three distinct categories (fit, unfit, and frail) based on age, activities of daily living (ADL), instrumental activities of daily living (IADL) and the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Participants will be assigned to Cohort A (unfit) or B (frail) using the sGA.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: ADC Therapeutics
- Phone Number: 954-903-7994
- Email: clinical.trials@adctherapeutics.com
Study Locations
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Alessandria, Italy, 15121
- Ospedaliera Santi Antonio E Biagio E Cesare Arrigo-SC Ematologia
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Brescia, Italy, 25123
- Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia
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Milano, Italy, 20122
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
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San Juan, Puerto Rico, 00919-1227
- Hospital Español Auxilio Mutuo
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Barcelona, Spain, 08003
- Hospital del Mar - Parc de Salut Mar
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Barcelona, Spain, 08908
- Institut Catala d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
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Cáceres, Spain, 10003
- Hospital San Pedro de Alcantara
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Madrid, Spain, 28034
- Hospital Universitario Ramón y Cajal
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Madrid, Spain, 28040
- Hospital Universitario Fundacion Jimenez Diaz
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València, Spain, 46015
- Hospital Arnau de Vilanova
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Cantabria
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Santander, Cantabria, Spain, 39008
- Hospital Universitario Marqués de Valdecilla
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Navarre
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Pamplona, Navarre, Spain, 31008
- Clinica Universidad de Navarra - Pamplona
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Arizona
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Tucson, Arizona, United States, 85724
- University of Arizona Cancer Center
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Arkansas
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Little Rock, Arkansas, United States, 72205
- Winthrop P. Rockefeller Cancer Institute
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Colorado
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Aurora, Colorado, United States, 80012
- Rocky Mountain Cancer Centers - Aurora
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Illinois
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Niles, Illinois, United States, 60714
- USOR - Illinois Cancer Specialists - Niles
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Kentucky
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Pikeville, Kentucky, United States, 41501
- Leonard Lawson Cancer Center
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Nevada
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Reno, Nevada, United States, 89511
- Cancer Care Specialists - Nevada
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New York
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Babylon, New York, United States, 11702
- New York Cancer & Blood Specialists - New Hyde Park
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Port Jefferson, New York, United States, 11776
- New York Cancer & Blood Specialists - Babylon Medical Oncology
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North Carolina
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Charlotte, North Carolina, United States, 28204
- Novant Health Cancer Specialists - Charlotte
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Ohio
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Cincinnati, Ohio, United States, 45236
- USOR - Oncology Hematology Care - Kenwood
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Cleveland, Ohio, United States, 44106
- University Hospitals Cleveland Medical Center
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Columbus, Ohio, United States, 43210
- Ohio Health - Research and Innovation Institute
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Oregon
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Eugene, Oregon, United States, 97401
- Willamette Valley Cancer Institute and Research Center - Eugene
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Pennsylvania
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Reading, Pennsylvania, United States, 19611
- Reading Hospital - Tower Health
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South Carolina
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Greenville, South Carolina, United States, 29605
- Prisma Health Cancer Institute
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South Dakota
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Sioux Falls, South Dakota, United States, 57105
- Avera Cancer Institute
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Texas
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Austin, Texas, United States, 78705
- Texas Oncology - Austin Midtown
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Dallas, Texas, United States, 75230
- Texas Oncology - Medical City Dallas
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Dallas, Texas, United States, 75231
- USOR - Texas Oncology - Presbyterian Cancer Center Dallas
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Dallas, Texas, United States, 75246
- USOR - Texas Oncology - Baylor Charles A. Sammons Cancer Center
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Houston, Texas, United States, 77030
- University of Texas MD Anderson Cancer Center
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San Antonio, Texas, United States, 78240
- USOR - Texas Oncology - San Antonio
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Tyler, Texas, United States, 75702
- Texas Oncology Northeast Texas - Tyler
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Virginia
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Blacksburg, Virginia, United States, 24060
- Blue Ridge Cancer Care - Blacksburg
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Gainesville, Virginia, United States, 20155
- USOR - Virginia Cancer Specialists - Gainesville Office
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Richmond, Virginia, United States, 23229
- Virginia Cancer Institute - West End
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Virginia Beach, Virginia, United States, 23456
- USOR - Virginia Oncology Associates
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Washington
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Richland, Washington, United States, 99352
- Kadlec Clinic - Hematology and Oncology
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Vancouver, Washington, United States, 98684
- USOR - Northwest Cancer Specialists, P.C. dba Compass Oncology - Vancouver Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Pathologic diagnosis of DLBCL, as defined by the 2016 World Health Organization (WHO) classification (including participants with DLBCL transformed from indolent lymphoma), or HGBCL, or Grade 3b FL.
- Measurable disease as defined by the 2014 Lugano Classification.
- Stages I-IV.
- ECOG PS 0-2; ECOG PS 3 allowed if decline in status is deemed related to lymphoma & felt to be potentially reversible by the treating physician.
Adequate organ function as defined by screening laboratory values within the following parameters:
- Absolute neutrophil count (ANC) ≥1.0 x 10^3/µL (off growth factors at least 72 hours).
- Platelet count ≥75 x 10^3/µL without transfusion in the past 7 days.
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤2.5 x the upper limit of normal (ULN).
- Total bilirubin ≤1.5 x ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 x ULN).
- Calculated creatinine clearance >30 mL/min by the Cockcroft and Gault equation.
Note: A laboratory assessment may be repeated a maximum of two times during the screening period to confirm eligibility.
- Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception from the time of giving informed consent until at least 12 months after the last dose of study treatment. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of the first dose until at least 7 months after the participant receives his last dose of study treatment.
Inclusion Criteria specific for Cohort A:
Unfit as defined by the simplified geriatric assessment (sGA). Includes all of the following:
- Aged ≥80 years
- ADL score of 6
- IADL score of 8
- CIRS-G: no score of 3-4 and <5 scores of 2
Inclusion Criteria specific for Cohort B:
Frail as defined by sGA:
- Aged ≥80 years
- ADL score of <6 and/or
- IADL score of <8 and/or
- CIRS-G: ≥1 score of 3-4 and/or >5 scores of 2 OR
Aged ≥65 - <80 with at least one of the following cardiac comorbidities that make anthracycline-containing regimens inadvisable as determined by the investigator.
- Left ventricular ejection fraction (LVEF) ≥30 to <50%
- History of myocardial infarction within 6 months prior to screening
- Ischemic heart disease
- History of stroke within 12 months prior to screening
Exclusion Criteria:
- Known history of hypersensitivity to or positive serum human anti-drug antibody to a cluster of differentiation 19 (CD19) antibody.
- Previous therapy for DLBCL, HGBCL, or Grade 3b FL (with exception of corticosteroid course for symptom management of less than 14 days).
- Previous therapy with loncastuximab tesirine and rituximab for any indication.
- Known history of hypersensitivity to any component of study treatment (loncastuximab tesirine and rituximab)
Human immunodeficiency virus (HIV) seropositive with any of the following:
- CD4+ T-cell (CD4+) counts <350 cells/µL
- Acquired immunodeficiency syndrome (AIDS) - defining opportunistic infection within 12 months prior to screening
- Not on anti-retroviral therapy, or on anti-retroviral therapy for <4 weeks at the time of screening
- HIV viral load ≥400 copies/mL
- Serologic evidence of chronic hepatitis B virus (HBV) infection and unable or unwilling to receive standard prophylactic antiviral therapy or with detectable HBV viral load.
- Serologic evidence of hepatitis C virus (HCV) infection without completion of curative treatment or with detectable HCV viral load.
- History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
- Lymphoma with active central nervous system involvement at the time of screening, including leptomeningeal disease.
- 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).
- Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy within 14 days prior to start of study drug (Cycle 1 Day 1 [C1D1]), except shorter if approved by the Sponsor.
- Use of any other experimental medication within 14 days prior to start of study drug (C1D1).
- Received live vaccine within 4 weeks of C1D1.
- Congenital long QT syndrome or a corrected Fridericia correction of the QT measure (QTcF) interval of >480 ms at screening (unless secondary to pacemaker or bundle branch block).
- 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.
- Any other significant medical illness, abnormality, or condition that would, in the Investigator's judgment, make the participant inappropriate for study participation or put the participant at risk.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Cohort A : Loncastuximab Tesirine + Rituximab (Lonca-R)
Participants who are unfit (per sGA) will receive Lonca-R for 3 cycles. Participants who achieve a complete response (CR) will receive Lonca-R for 1 additional cycle. Participants who achieve a partial response (PR) will receive Lonca-R for 3 additional cycles. Lonca-R will be administered as rituximab 375 mg/m^2 on Day 1 of Cycle 1 and loncastuximab tesirine 150 µg/kg on Day 2 of Cycle 1. During Cycle 2, Lonca-R will be administered as rituximab* 375 mg/m^2 and loncastuximab tesirine 150 µg/kg on Day 1. For cycles 3 and beyond, Lonca-R will be administered as rituximab 375 mg/m^2 and loncastuximab tesirine 75 µg/kg on Day 1. *subcutaneous rituximab 1400mg/dose may be used during Cycle 2 and beyond |
Intravenous (IV) Infusion
Other Names:
Cycle 1 - Intravenous (IV) Infusion.
Cycle 2+ - Intravenous (IV) Infusion or Subcutaneous (SC) Administration.
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Experimental: Cohort B : Loncastuximab Tesirine + Rituximab (Lonca-R)
Participants who are frail (per sGA) or participants with cardiac comorbidities will receive Lonca-R for 3 cycles. Participants who achieve a CR will receive Lonca-R for 1 additional cycle. Participants who achieve a PR will receive Lonca-R for 3 additional cycles for a total of up to 6 cycles. Only participants enrolled in Cohort B, who achieve stable disease (SD) and deriving clinical benefit per the treating physician, may also receive Lonca-R for an additional 3 cycles. Lonca-R will be administered as rituximab 375 mg/m^2 on Day 1 of Cycle 1 and loncastuximab tesirine 150 µg/kg on Day 2 of Cycle 1. During Cycle 2, Lonca-R will be administered as rituximab* 375 mg/m^2 and loncastuximab tesirine 150 µg/kg on Day 1. For cycles 3 and beyond, Lonca-R will be administered as rituximab 375 mg/m^2 and loncastuximab tesirine 75 µg/kg on Day 1. *subcutaneous rituximab 1400mg/dose may be used during Cycle 2 and beyond |
Intravenous (IV) Infusion
Other Names:
Cycle 1 - Intravenous (IV) Infusion.
Cycle 2+ - Intravenous (IV) Infusion or Subcutaneous (SC) Administration.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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CR Rate
Time Frame: Up to 5.5 years
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Up to 5.5 years
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Cohort B: Percentage of Participants Completing 4 Cycles of Treatment
Time Frame: Up to 12 weeks
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Up to 12 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall Response Rate (ORR)
Time Frame: Up to 22 weeks
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Up to 22 weeks
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2-year Progression-free Survival (PFS)
Time Frame: Up to 2 years
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Up to 2 years
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3-year Overall Survival (OS)
Time Frame: Up to 3 years
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Up to 3 years
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Duration of Response (DoR)
Time Frame: Up to 5.5 years
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Up to 5.5 years
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Number of Participants who Experience a Treatment-emergent Adverse Event
Time Frame: Up to 5.5 years
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Includes frequency and severity of adverse events (AEs) and serious AEs (SAEs) that occur after study treatment administration.
Clinically significant changes from baseline in safety laboratory variables, vital signs and physical examinations will also be recorded as TEAEs/SAEs.
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Up to 5.5 years
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Number of Participants with a Clinically Significant Change from Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Score
Time Frame: Baseline up to 22 weeks
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ECOG performance status will be assessed on a 6-point scale ranging from 0 (fully active) to 5 (dead).
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Baseline up to 22 weeks
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Serum Concentration of Loncastuximab Tesirine Pyrrolobenzodiazepine (PBD)-conjugated Antibody
Time Frame: Up to 2 years
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Up to 2 years
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Serum Concentration of SG3199 Unconjugated Warhead
Time Frame: Up to 2 years
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Up to 2 years
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Serum Concentration of Total Antibody
Time Frame: Up to 2 years
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Up to 2 years
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Number of Participants with Confirmed Positive Anti-Drug Antibody (ADA) Responses
Time Frame: Up to 2 years
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Up to 2 years
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Number of Participants with a Change from Baseline in Patient-reported Outcomes
Time Frame: Baseline up to 22 weeks
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Includes changes in symptoms, functions and overall health status as measured by the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym).
The FACT-Lym is scored from 0-168 where a higher score indicates a worse outcome.
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Baseline up to 22 weeks
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
- Loncastuximab tesirine
Other Study ID Numbers
- ADCT-402-203
- 2021-005312-57 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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