Diffuse Large B-cell LymphomaPhase 2LOTIS-9NCT05144009
A Study of Loncastuximab Tesirine and Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Participants With Diffuse Large B-cell Lymphoma (DLBCL)
A Phase 2 study testing Loncastuximab Tesirine and Rituximab in people with Diffuse Large B-cell Lymphoma, run by ADC Therapeutics S.A. at 41 sites in 4 countries.
Trial summary
The main objective of the trial is to assess the efficacy and tolerability of Lonca-R in unfit and frail participants with previously untreated DLBCL. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Diffuse Large B-cell Lymphoma
- What is being tested?
- Loncastuximab Tesirine and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 41 sitesin 4 countries
- Study dates
- 21 Jun 2022to 22 Jan 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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).
Show all 27Show fewer
- 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.
- 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
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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.
Trial locations and contacts
41 sites in 4 countries.
41 sites in 4 countries
United States29 sites
Rocky Mountain Cancer Centers - Aurora
Aurora, Colorado, 80012
Texas Oncology - Austin Midtown
Austin, Texas, 78705
New York Cancer & Blood Specialists - New Hyde Park
Babylon, New York, 11702
Blue Ridge Cancer Care - Blacksburg
Blacksburg, Virginia, 24060
Novant Health Cancer Specialists - Charlotte
Charlotte, North Carolina, 28204
USOR - Oncology Hematology Care - Kenwood
Cincinnati, Ohio, 45236
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Ohio Health - Research and Innovation Institute
Columbus, Ohio, 43210
Texas Oncology - Medical City Dallas
Dallas, Texas, 75230
USOR - Texas Oncology - Presbyterian Cancer Center Dallas
Dallas, Texas, 75231
USOR - Texas Oncology - Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
Willamette Valley Cancer Institute and Research Center - Eugene
Eugene, Oregon, 97401
USOR - Virginia Cancer Specialists - Gainesville Office
Gainesville, Virginia, 20155
Prisma Health Cancer Institute
Greenville, South Carolina, 29605
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Winthrop P. Rockefeller Cancer Institute
Little Rock, Arkansas, 72205
USOR - Illinois Cancer Specialists - Niles
Niles, Illinois, 60714
Leonard Lawson Cancer Center
Pikeville, Kentucky, 41501
New York Cancer & Blood Specialists - Babylon Medical Oncology
Port Jefferson, New York, 11776
Reading Hospital - Tower Health
Reading, Pennsylvania, 19611
Cancer Care Specialists - Nevada
Reno, Nevada, 89511
Kadlec Clinic - Hematology and Oncology
Richland, Washington, 99352
Virginia Cancer Institute - West End
Richmond, Virginia, 23229
USOR - Texas Oncology - San Antonio
San Antonio, Texas, 78240
Avera Cancer Institute
Sioux Falls, South Dakota, 57105
University of Arizona Cancer Center
Tucson, Arizona, 85724
Texas Oncology Northeast Texas - Tyler
Tyler, Texas, 75702
USOR - Northwest Cancer Specialists, P.C. dba Compass Oncology - Vancouver Cancer Center
Vancouver, Washington, 98684
USOR - Virginia Oncology Associates
Virginia Beach, Virginia, 23456
Spain8 sites
Hospital del Mar - Parc de Salut Mar
Barcelona, 08003
Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
Barcelona, 08908
Hospital San Pedro de Alcantara
Cáceres, 10003
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040
Clinica Universidad de Navarra - Pamplona
Pamplona, Navarre, 31008
Hospital Universitario Marqués de Valdecilla
Santander, Cantabria, 39008
Hospital Arnau de Vilanova
Valencia, 46015
Italy3 sites
Ospedaliera Santi Antonio E Biagio E Cesare Arrigo-SC Ematologia
Alessandria, 15121
Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia
Brescia, 25123
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, 20122
About this study
Official title: 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)
The main objective of the trial is to assess the efficacy and tolerability of Lonca-R in unfit and frail participants with previously untreated DLBCL.
Read the 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.
- Conditions
- Diffuse Large B-cell Lymphoma
- Being tested
- Loncastuximab Tesirine, Rituximab
- Keywords
- Lymphoma, Loncastuximab Tesirine, Rituximab, Non-Hodgkin's lymphoma, Elderly, R-mini-CHOP, Geriatric Assessment, FIL Tool, Unfit, Frail
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Loncastuximab TesirineDrug
Also called Zynlonta, ADCT-402
Intravenous (IV) Infusion
RituximabDrug
Cycle 1 - Intravenous (IV) Infusion. Cycle 2+ - Intravenous (IV) Infusion or Subcutaneous (SC) Administration.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A : Loncastuximab Tesirine + Rituximab (Lonca-R) | Experimental | 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 Receives: Drug: Loncastuximab Tesirine; Drug: Rituximab |
| Cohort B : Loncastuximab Tesirine + Rituximab (Lonca-R) | Experimental | 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 Receives: Drug: Loncastuximab Tesirine; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
CR Rate
Defined as percentage of participants with a best overall response (BOR) of CR as determined by the Investigator according to the 2014 Lugano Classification criteria.
CR was defined as achieving:
- Complete metabolic response for positron emission tomography (PET)-computed tomography (CT) OR
- Complete radiologic response (target node regress to <1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology) for CT if disease was not fluorodeoxyglucose (FDG)-avid at baseline.
Measured: Up to a maximum of 17.1 months
Cohort B: Percentage of Participants Who Completed 4 Cycles of Treatment
Defined by the number of participants who completed a total of 4 cycles of therapy divided by the total number of participants * 100.
Measured: Up to 12 weeks (3 week cycle length)
Secondary outcomes (11)
Overall Response Rate (ORR)
Defined as the percentage of participants who achieved either CR or PR as BOR as determined by Investigator according to the 2014 Lugano Classification criteria.
CR was defined as achieving:
- Complete metabolic response for PET-CT OR
- Complete radiologic response (target node regress to <1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology) for CT if disease was not FDG-avid at baseline.
PR was defined as achieving:
- Partial metabolic response (findings indicate residual disease) for PET-CT OR
- Partial remission (>50% decrease in target measurable nodes, regression/ absence/ no increase of non-measured lesions, spleen regressed by >50% in length and no new lesions) for CT if disease was not FDG-avid at baseline.
Measured: Up to a maximum of 17.1 months
2-year Progression-free Survival (PFS)
PFS was defined as the time from first dose of study drug until the first date of either disease progression (PD) or death due to any cause. The 2-year PFS was defined as the percentage of participants that were PFS event-free at 2 years per investigator assessment with 95% confidence interval (CI) estimated using Kaplan-Meier method.
Measured: 2 years
3-year Overall Survival (OS)
OS was defined as the time from randomization date until death due to any cause. The 3-year OS was defined as the percentage of participants that were OS event-free at 3 years with 95% CI estimated using Kaplan-Meier method.
Measured: 3 years
Duration of Response (DoR)
Defined for participants with CR or PR only as the interval between the date of initial documentation of a response and the date of the first documented progressive disease (based on radiographic or clinical progression at end of study or death due to any cause, whichever occurred first) per investigator assessment with 95% CI estimated using Kaplan-Meier method.
CR was defined as achieving:
- Complete metabolic response for PET-CT OR
- Complete radiologic response (target node regress to <1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology) for CT if disease was not FDG-avid at baseline.
PR was defined as achieving:
- Partial metabolic response (findings indicate residual disease) for PET-CT OR
- Partial remission (>50% decrease in target measurable nodes, regression/ absence/ no increase of non-measured lesions, spleen regressed by >50% in length and no new lesions) for CT if disease was not FDG-avid at baseline.
Measured: Up to a maximum of 17.1 months
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product. A TEAE was defined as an AE that occurred or worsened in the period extending from the first dose of study drug to 15 weeks after the last dose of study drugs in this study or start of a new anticancer therapy, whichever was earlier. A serious AE (SAE) was defined as an AE that resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or an important medical event. A severe AE was defined as Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade 3 (severe) or above.
Clinically significant changes in safety laboratory variables, vital signs, physical examinations, and Eastern Cooperative Oncology Group performance score were recorded as AEs.
Measured: Up to approximately 8 months
Maximum Observed Concentration (Cmax) of Conjugated Antibody
Pharmacokinetic (PK) was assessed by a central laboratory using validated bioanalytical methods. Analysis considered model development for conjugated antibodies and total antibodies only, as pre-specified in protocol section 9.9.
Measured: Cycle 1 Day 2: predose (preferably within 2 h prior to start of infusion) and at the end (within -5 to +10 min) of loncastuximab tesirine infusion; Cycles 2-6 Day 1 predose and at the end of loncastuximab tesirine infusion (3 week cycle length)
Cmax of Total Antibody
PK was assessed by a central laboratory using validated bioanalytical methods. Analysis considered model development for conjugated antibodies and total antibodies only, as pre-specified in protocol section 9.9.
Measured: Cycle 1 Day 2: predose (preferably within 2 h prior to start of infusion) and at the end (within -5 to +10 min) of loncastuximab tesirine infusion; Cycles 2-6 Day 1 predose and at the end of loncastuximab tesirine infusion (3 week cycle length)
Trough Concentration (Ctrough) of Conjugated Antibody
PK was assessed by a central laboratory using validated bioanalytical methods. Analysis considered model development for conjugated antibodies and total antibodies only, as pre-specified in protocol section 9.9.
Measured: Cycle 1 Day 2: predose (preferably within 2 h prior to start of infusion); Cycles 2-6 Day 1 predose (3 week cycle length)
Ctrough of Total Antibody
PK was assessed by a central laboratory using validated bioanalytical methods. Analysis considered model development for conjugated antibodies and total antibodies only, as pre-specified in protocol section 9.9.
Measured: Cycle 1 Day 2: predose (preferably within 2 h prior to start of infusion); Cycles 2-6 Day 1 predose (3 week cycle length)
Number of Participants With Confirmed Positive Anti-Drug Antibody (ADA) Response
Detection of ADAs against loncastuximab tesirine was performed by using a screening assay for identification of antibody positive samples/participants and a confirmation assay. A participant was considered to have an ADA response if ADA sample was positive at any pre-specified, post-treatment timepoint.
Measured: Cycle 1 Day 2 pre-dose (preferably within 2 h prior to start of infusion) then Day 1 pre-dose of Cycles 2, 4, and 6 (3 week cycle length)
Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale and Composite Scores
The following score ranges were possible for the FACT-Lym subscale and composite scores, with higher scores indicating better quality of life/outcome: 0 to 28 for physical well-being, social/family well-being, and functional well-being; 0 to 24 for emotional well-being; 0 to 60 for lymphoma subscale score; 0 to 116 for FACT-Lym trial outcome index; 0 to 108 for FACT-G total score; and 0 to 168 for FACT-Lym Total. An increase in subscale/composite scores from Baseline indicated better quality of life/outcome.
Measured: Baseline and End of Treatment Visit (a maximum of 19 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2021
- Study start21 Jun 2022
- Primary completion22 Jan 2024
- Study completion22 Jan 2024
Why it stopped: The benefit-risk profile does not support continuation of the LOTIS-9 trial.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B-cell LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- ADC Therapeutics S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05144009
- Sponsor's protocol ID
- ADCT-402-203
- Other IDs
- 2021-005312-57, 2022-501601-12-00
- Acronym
- LOTIS-9
- Status last verified
- Jan 2025
- First submitted
- 22 Nov 2021
- Last updated
- 30 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nair R, Kumar A, Chapman AE, Levy MY, Sharman JP, Choudhary Y, Jehangir W, Melear JM, Urban A, Niewarowski A, Wang L, Toukam M, Burke JM, Westin JR. Loncastuximab and Rituximab in Elderly Unfit/Frail Patients With Previously Untreated Diffuse Large B-Cell Lymphoma. Blood Adv. 2026 Oct 15:bloodadvances.2026020494. doi: 10.1182/bloodadvances.2026020494. Online ahead of print.
PubMed 42879743
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05144009
- Acronym / sponsor ID
- LOTIS-9 / ADCT-402-203
- Conditions
- Diffuse Large B-cell Lymphoma
- Keywords
- Lymphoma, Loncastuximab Tesirine, Rituximab, Non-Hodgkin's lymphoma, Elderly, R-mini-CHOP, Geriatric Assessment, FIL Tool
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The benefit-risk profile does not support continuation of the LOTIS-9 trial.
- Enrolment
- 41 participants (actual)
- Lead sponsor
- ADC Therapeutics S.A.Industry (pharma, biotech, devices)
- Study start
- 21 Jun 2022 (actual)
- Primary completion
- 22 Jan 2024 (actual)
- Study completion
- 22 Jan 2024 (actual)
- First posted
- 3 Dec 2021 (actual)
- Results
- Posted 30 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objective of the trial is to assess the efficacy and tolerability of Lonca-R in unfit and frail participants with previously untreated DLBCL.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A : Loncastuximab Tesirine + Rituximab (Lonca-R) | Experimental | Drug: Loncastuximab Tesirine, Drug: RituximabParticipants 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 |
| Cohort B : Loncastuximab Tesirine + Rituximab (Lonca-R) | Experimental | Drug: Loncastuximab Tesirine, Drug: RituximabParticipants 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 |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (27 listed)
- 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:
Key exclusion criteria (20 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Loncastuximab TesirineAlso: Zynlonta, ADCT-402Intravenous (IV) Infusion | Drug | Cohort A : Loncastuximab Tesirine + Rituximab (Lonca-R), Cohort B : Loncastuximab Tesirine + Rituximab (Lonca-R) |
| RituximabCycle 1 - Intravenous (IV) Infusion. Cycle 2+ - Intravenous (IV) Infusion or Subcutaneous (SC) Administration. | Drug | Cohort A : Loncastuximab Tesirine + Rituximab (Lonca-R), Cohort B : Loncastuximab Tesirine + Rituximab (Lonca-R) |
Primary outcome
CR Rate
Time frame: Up to a maximum of 17.1 months
Defined as percentage of participants with a best overall response (BOR) of CR as determined by the Investigator according to the 2014 Lugano Classification criteria. CR was defined as achieving: * Complete metabolic response for positron emission tomography (PET)-computed tomography (CT) OR * Complete radiologic response (target node regress to <1.5 cm, no non-measured lesions, no organ enlargement, no new lesions and normal bone marrow morphology) for CT if disease was not fluorodeoxyglucose (FDG)-avid at baseline.
Cohort B: Percentage of Participants Who Completed 4 Cycles of Treatment
Time frame: Up to 12 weeks (3 week cycle length)
Defined by the number of participants who completed a total of 4 cycles of therapy divided by the total number of participants * 100.
11 secondary outcomes
Overall Response Rate (ORR)
Time frame: Up to a maximum of 17.1 months
2-year Progression-free Survival (PFS)
Time frame: 2 years
3-year Overall Survival (OS)
Time frame: 3 years
Duration of Response (DoR)
Time frame: Up to a maximum of 17.1 months
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Time frame: Up to approximately 8 months
Maximum Observed Concentration (Cmax) of Conjugated Antibody
Time frame: Cycle 1 Day 2: predose (preferably within 2 h prior to start of infusion) and at the end (within -5 to +10 min) of loncastuximab tesirine infusion; Cycles 2-6 Day 1 predose and at the end of loncastuximab tesirine infusion (3 week cycle length)
Cmax of Total Antibody
Time frame: Cycle 1 Day 2: predose (preferably within 2 h prior to start of infusion) and at the end (within -5 to +10 min) of loncastuximab tesirine infusion; Cycles 2-6 Day 1 predose and at the end of loncastuximab tesirine infusion (3 week cycle length)
Trough Concentration (Ctrough) of Conjugated Antibody
Time frame: Cycle 1 Day 2: predose (preferably within 2 h prior to start of infusion); Cycles 2-6 Day 1 predose (3 week cycle length)
Ctrough of Total Antibody
Time frame: Cycle 1 Day 2: predose (preferably within 2 h prior to start of infusion); Cycles 2-6 Day 1 predose (3 week cycle length)
Number of Participants With Confirmed Positive Anti-Drug Antibody (ADA) Response
Time frame: Cycle 1 Day 2 pre-dose (preferably within 2 h prior to start of infusion) then Day 1 pre-dose of Cycles 2, 4, and 6 (3 week cycle length)
Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale and Composite Scores
Time frame: Baseline and End of Treatment Visit (a maximum of 19 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42879743Nair R, Kumar A, Chapman AE, Levy MY, Sharman JP, Choudhary Y, Jehangir W, Melear JM, Urban A, Niewarowski A, Wang L, Toukam M, Burke JM, Westin JR. Loncastuximab and Rituximab in Elderly Unfit/Frail Patients With Previously Untreated Diffuse Large B-Cell Lymphoma. Blood Adv. 2026 Oct 15:bloodadvances.2026020494. doi: 10.1182/bloodadvances.2026020494. Online ahead of print.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
41 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Loncastuximab Tesirine and Rituximab in people with Diffuse Large B-cell Lymphoma, run by ADC Therapeutics S.A. at 41 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 27 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 41 sites in United States, Spain, Italy, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CR Rate (time frame: Up to a maximum of 17.1 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05144009, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2025.