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)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Diffuse Large B-cell Lymphoma
Keywords: Lymphoma
Loncastuximab Tesirine
Rituximab
Non-Hodgkin's lymphoma
Elderly
R-mini-CHOP
Geriatric Assessment
FIL Tool
Unfit
Frail
Lead sponsor: ADC Therapeutics S.A.
Sponsor class: INDUSTRY
First posted: 2021-12-03
Enrollment: 41
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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:

  1. Absolute neutrophil count (ANC) ≥1.0 x 10\^3/µL (off growth factors at least 72 hours).
  2. Platelet count ≥75 x 10\^3/µL without transfusion in the past 7 days.
  3. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) ≤2.5 x the upper limit of normal (ULN).
  4. Total bilirubin ≤1.5 x ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 x ULN).
  5. 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:

  1. Aged ≥80 years
  2. ADL score of 6
  3. IADL score of 8
  4. CIRS-G: no score of 3-4 and \<5 scores of 2

Inclusion Criteria specific for Cohort B:

* Frail as defined by sGA:

  1. Aged ≥80 years
  2. ADL score of \<6 and/or
  3. IADL score of \<8 and/or
  4. 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.

  1. Left ventricular ejection fraction (LVEF) ≥30 to \<50%
  2. History of myocardial infarction within 6 months prior to screening
  3. Ischemic heart disease
  4. 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:

  1. CD4+ T-cell (CD4+) counts \<350 cells/µL
  2. Acquired immunodeficiency syndrome (AIDS) - defining opportunistic infection within 12 months prior to screening
  3. Not on anti-retroviral therapy, or on anti-retroviral therapy for \<4 weeks at the time of screening
  4. 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.

Primary outcomes:
measure: CR Rate
timeFrame: Up to a maximum of 17.1 months
measure: Cohort B: Percentage of Participants Who Completed 4 Cycles of Treatment
timeFrame: Up to 12 weeks (3 week cycle length)
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to a maximum of 17.1 months
measure: 2-year Progression-free Survival (PFS)
timeFrame: 2 years
measure: 3-year Overall Survival (OS)
timeFrame: 3 years
measure: Duration of Response (DoR)
timeFrame: Up to a maximum of 17.1 months
measure: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
timeFrame: Up to approximately 8 months
measure: Maximum Observed Concentration (Cmax) of Conjugated Antibody
timeFrame: 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)
measure: Cmax of Total Antibody
timeFrame: 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)
measure: Trough Concentration (Ctrough) of Conjugated Antibody
timeFrame: Cycle 1 Day 2: predose (preferably within 2 h prior to start of infusion); Cycles 2-6 Day 1 predose (3 week cycle length)
measure: Ctrough of Total Antibody
timeFrame: Cycle 1 Day 2: predose (preferably within 2 h prior to start of infusion); Cycles 2-6 Day 1 predose (3 week cycle length)
measure: Number of Participants With Confirmed Positive Anti-Drug Antibody (ADA) Response
timeFrame: 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)
measure: Change From Baseline in Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) Subscale and Composite Scores
timeFrame: Baseline and End of Treatment Visit (a maximum of 19 weeks)
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Little Rock
country: United States
facility: Winthrop P. Rockefeller Cancer Institute
state: Arkansas
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers - Aurora
state: Colorado
city: Niles
country: United States
facility: USOR - Illinois Cancer Specialists - Niles
state: Illinois
city: Pikeville
country: United States
facility: Leonard Lawson Cancer Center
state: Kentucky
city: Reno
country: United States
facility: Cancer Care Specialists - Nevada
state: Nevada
city: Babylon
country: United States
facility: New York Cancer & Blood Specialists - New Hyde Park
state: New York
city: Port Jefferson
country: United States
facility: New York Cancer & Blood Specialists - Babylon Medical Oncology
state: New York
city: Charlotte
country: United States
facility: Novant Health Cancer Specialists - Charlotte
state: North Carolina
city: Cincinnati
country: United States
facility: USOR - Oncology Hematology Care - Kenwood
state: Ohio
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio Health - Research and Innovation Institute
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center - Eugene
state: Oregon
city: Reading
country: United States
facility: Reading Hospital - Tower Health
state: Pennsylvania
city: Greenville
country: United States
facility: Prisma Health Cancer Institute
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Cancer Institute
state: South Dakota
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Medical City Dallas
state: Texas
city: Dallas
country: United States
facility: USOR - Texas Oncology - Presbyterian Cancer Center Dallas
state: Texas
city: Dallas
country: United States
facility: USOR - Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: San Antonio
country: United States
facility: USOR - Texas Oncology - San Antonio
state: Texas
city: Tyler
country: United States
facility: Texas Oncology Northeast Texas - Tyler
state: Texas
city: Blacksburg
country: United States
facility: Blue Ridge Cancer Care - Blacksburg
state: Virginia
city: Gainesville
country: United States
facility: USOR - Virginia Cancer Specialists - Gainesville Office
state: Virginia
city: Richmond
country: United States
facility: Virginia Cancer Institute - West End
state: Virginia
city: Virginia Beach
country: United States
facility: USOR - Virginia Oncology Associates
state: Virginia
city: Richland
country: United States
facility: Kadlec Clinic - Hematology and Oncology
state: Washington
city: Vancouver
country: United States
facility: USOR - Northwest Cancer Specialists, P.C. dba Compass Oncology - Vancouver Cancer Center
state: Washington
city: Alessandria
country: Italy
facility: Ospedaliera Santi Antonio E Biagio E Cesare Arrigo-SC Ematologia
city: Brescia
country: Italy
facility: Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
city: San Juan
country: Puerto Rico
facility: Hospital Español Auxilio Mutuo
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabria
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona
state: Navarre
city: Barcelona
country: Spain
facility: Hospital del Mar - Parc de Salut Mar
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: València
country: Spain
facility: Hospital Arnau de Vilanova
Study officials:
References: