A Study of Loncastuximab Tesirine and Rituximab (Lonca-R) in Previously Untreated Unfit/Frail Participants With Diffuse Large B-cell Lymphoma (DLBCL)

Diffuse Large B-cell Lymphoma Clinical Trial

— LOTIS-9  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05144009
• Other study ID #: ADCT-402-203
• Secondary ID: 2021-005312-57
• Status: Completed
• Phase: Phase 2
• Start date: June 21, 2022
• Est. completion date: January 22, 2024

Study information

• Verified date: January 2024
• Source: ADC Therapeutics S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: January 22, 2024
• Est. primary completion date: January 22, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 80 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Loncastuximab Tesirine
Intravenous (IV) Infusion
• Rituximab
Cycle 1 - Intravenous (IV) Infusion. Cycle 2+ - Intravenous (IV) Infusion or Subcutaneous (SC) Administration.

Locations

Country	Name	City	State
Italy	Ospedaliera Santi Antonio E Biagio E Cesare Arrigo-SC Ematologia	Alessandria
Italy	Azienda Socio Sanitaria Territoriale (ASST) degli Spedali Civili di Brescia	Brescia
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milano
Puerto Rico	Hospital Español Auxilio Mutuo	San Juan
Spain	Hospital del Mar - Parc de Salut Mar	Barcelona
Spain	Institut Català d'Oncologia - Hospital Duran i Reynals (ICO L'Hospitalet)	Barcelona
Spain	Hospital San Pedro de Alcantara	Cáceres
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Clinica Universidad de Navarra - Pamplona	Pamplona	Navarre
Spain	Hospital Universitario Marqués de Valdecilla	Santander	Cantabria
Spain	Hospital Arnau de Vilanova	València
United States	Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado
United States	Texas Oncology - Austin Midtown	Austin	Texas
United States	New York Cancer & Blood Specialists - New Hyde Park	Babylon	New York
United States	Blue Ridge Cancer Care - Blacksburg	Blacksburg	Virginia
United States	Novant Health Cancer Specialists - Charlotte	Charlotte	North Carolina
United States	USOR - Oncology Hematology Care - Kenwood	Cincinnati	Ohio
United States	University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Ohio Health - Research and Innovation Institute	Columbus	Ohio
United States	Texas Oncology - Medical City Dallas	Dallas	Texas
United States	USOR - Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	USOR - Texas Oncology - Presbyterian Cancer Center Dallas	Dallas	Texas
United States	Willamette Valley Cancer Institute and Research Center - Eugene	Eugene	Oregon
United States	USOR - Virginia Cancer Specialists - Gainesville Office	Gainesville	Virginia
United States	Prisma Health Cancer Institute	Greenville	South Carolina
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Winthrop P. Rockefeller Cancer Institute	Little Rock	Arkansas
United States	USOR - Illinois Cancer Specialists - Niles	Niles	Illinois
United States	Leonard Lawson Cancer Center	Pikeville	Kentucky
United States	New York Cancer & Blood Specialists - Babylon Medical Oncology	Port Jefferson	New York
United States	Reading Hospital - Tower Health	Reading	Pennsylvania
United States	Cancer Care Specialists - Nevada	Reno	Nevada
United States	Kadlec Clinic - Hematology and Oncology	Richland	Washington
United States	Virginia Cancer Institute - West End	Richmond	Virginia
United States	USOR - Texas Oncology - San Antonio	San Antonio	Texas
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	University of Arizona Cancer Center	Tucson	Arizona
United States	Texas Oncology Northeast Texas - Tyler	Tyler	Texas
United States	USOR - Northwest Cancer Specialists, P.C. dba Compass Oncology - Vancouver Cancer Center	Vancouver	Washington
United States	USOR - Virginia Oncology Associates	Virginia Beach	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
ADC Therapeutics S.A.

Countries where clinical trial is conducted

United States,  Italy,  Puerto Rico,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CR Rate		Up to 5.5 years
Primary	Cohort B: Percentage of Participants Completing 4 Cycles of Treatment		Up to 12 weeks
Secondary	Overall Response Rate (ORR)		Up to 22 weeks
Secondary	2-year Progression-free Survival (PFS)		Up to 2 years
Secondary	3-year Overall Survival (OS)		Up to 3 years
Secondary	Duration of Response (DoR)		Up to 5.5 years
Secondary	Number of Participants who Experience a Treatment-emergent Adverse Event	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.	Up to 5.5 years
Secondary	Number of Participants with a Clinically Significant Change from Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Score	ECOG performance status will be assessed on a 6-point scale ranging from 0 (fully active) to 5 (dead).	Baseline up to 22 weeks
Secondary	Serum Concentration of Loncastuximab Tesirine Pyrrolobenzodiazepine (PBD)-conjugated Antibody		Up to 2 years
Secondary	Serum Concentration of SG3199 Unconjugated Warhead		Up to 2 years
Secondary	Serum Concentration of Total Antibody		Up to 2 years
Secondary	Number of Participants with Confirmed Positive Anti-Drug Antibody (ADA) Responses		Up to 2 years
Secondary	Number of Participants with a Change from Baseline in Patient-reported Outcomes	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.	Baseline up to 22 weeks