A Study to Evaluate the Pharmacokinetics and Safety of Loncastuximab Tesirine in Participants With Relapsed or Refractory Diffuse Large B-cell Lymphoma or High-grade B-cell Lymphoma With Hepatic Impairment (LOTIS-10)
- Conditions
- High-grade B-cell LymphomaDiffuse Large B-Cell Lymphoma
- Interventions
- Registration Number
- NCT05660395
- Lead Sponsor
- ADC Therapeutics S.A.
- Brief Summary
The primary objective of this study is to determine the recommended dosing regimen of loncastuximab tesirine in diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL) participants with moderate and severe hepatic impairment.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 56
-
Male or female participants aged 18 years or older
-
Pathologic diagnosis of relapsed (disease that has recurred following a response) or refractory (disease that failed to respond to prior therapy) DLBCL not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma (2016 World Health Organization classification) who have received at least one systemic treatment regimen
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Measurable disease as defined by the 2014 Lugano Classification
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Normal hepatic function or hepatic impairment as defined by the National Cancer Institute Organ Dysfunction Working Group hepatic impairment classification:
- Arm A Normal hepatic function: bilirubin and aspartate aminotransferase (AST) ≤ upper limit of normal (ULN)
- Arm B Moderate hepatic impairment: bilirubin > 1.5 × to 3 × ULN (any AST)
- Arm C Severe hepatic impairment: bilirubin > 3 × ULN (any AST)
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ECOG performance status 0 to 2 for participants with normal hepatic function. ECOG 0 to 3 for participants with moderate or severe hepatic impairment
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Adequate organ function
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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 10 months after the last dose of study drug. 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 last dose of study drug.
- Previous therapy with loncastuximab tesirine
- Allogenic or autologous stem cell transplant within 60 days prior to start of study drug (C1D1)
- Human immunodeficiency virus (HIV) seropositive
- 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
- Breastfeeding or pregnant
- Significant medical comorbidities
- Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy, within 14 days prior to start of study drug (C1D1), except shorter if approved by the Sponsor
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Normal Hepatic Function Loncastuximab Tesirine Participants will receive loncastuximab tesirine 0.15 mg/kg once every 3 weeks (Q3W) for two cycles, then 0.075 mg/kg Q3W for subsequent cycles (1 cycle = 21 days). Participants who have a toxicity meeting the criteria for dose reduction will have subsequent doses reduced by 50%. If the toxicity recurs, subsequent doses must be reduced by an additional 50%. A maximum of 2 dose reductions are allowed. Participants who have a toxicity meeting the criteria for dose reduction following Cycle 2 will receive the protocol-specified dose of 50% of initiate dose for Cycle 3, i.e., they will not have an additional dose reduction for Cycle 3. Arm B: Moderate Hepatic Impairment Loncastuximab Tesirine Participants will receive loncastuximab tesirine in a standard 3+3 dose-escalation design. Initial dose will be 0.09 mg/kg Q3W for two cycles, then 0.045 mg/kg Q3W for subsequent cycles (1 cycle = 21 days). The highest dose possibly administered will be 0.15 mg/kg Q3W. Participants who have a toxicity meeting the criteria for dose reduction will have subsequent doses reduced by 50%. If the toxicity recurs, subsequent doses must be reduced by an additional 50%. A maximum of 2 dose reductions are allowed. Participants who have a toxicity meeting the criteria for dose reduction following Cycle 2 will receive the protocol-specified dose of 50% of initiate dose for Cycle 3, i.e., they will not have an additional dose reduction for Cycle 3. Arm C: Severe Hepatic Impairment Loncastuximab Tesirine Participants will receive loncastuximab tesirine in a standard 3+3 dose-escalation design. Initial dose will be 0.09 mg/kg Q3W for two cycles, then 0.045 mg/kg Q3W for subsequent cycles (1 cycle = 21 days). The highest dose possibly administered will be 0.15 mg/kg Q3W. Participants who have a toxicity meeting the criteria for dose reduction will have subsequent doses reduced by 50%. If the toxicity recurs, subsequent doses must be reduced by an additional 50%. A maximum of 2 dose reductions are allowed. Participants who have a toxicity meeting the criteria for dose reduction following Cycle 2 will receive the protocol-specified dose of 50% of initiate dose for Cycle 3, i.e., they will not have an additional dose reduction for Cycle 3.
- Primary Outcome Measures
Name Time Method Number of Participants with Moderate or Severe Hepatic Impairment Who Experience a Dose-Limiting Toxicity (DLT) Day 1 to Day 21 of Cycle 1, where a cycle is 21 days
- Secondary Outcome Measures
Name Time Method Maximum Concentration (Cmax) of Loncastuximab Tesirine and SG3199 in Serum Day 1 up to 1 year Area Under the Concentration-time Curve from Time Zero to the Last Quantifiable Concentration (AUClast) of Loncastuximab Tesirine and SG3199 in Serum Day 1 up to 1 year Accumulation Index (AI) of Loncastuximab Tesirine and SG3199 in Serum Day 1 up to 1 year Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) Up to approximately 1 year Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Reduction Up to approximately 1 year Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Signs Baseline up to approximately 1 year Number of Participants Who Experience a Clinically Significant Change from Baseline in 12-Lead Electrocardiogram (ECG) Measurements Baseline up to approximately 1 year Number of Participants With Anti-drug Antibody (ADA) Titers to Loncastuximab Tesirine Day 1 up to 1 year Area Under the Concentration-time Curve from Time Zero to the End of the Dosing Interval (AUCtau) of Loncastuximab Tesirine and SG3199 in Serum Day 1 up to 1 year Apparent Terminal Elimination Half-life (Thalf) of Loncastuximab Tesirine and SG3199 in Serum Day 1 up to 1 year Apparent Clearance (CL) of Loncastuximab Tesirine and SG3199 in Serum Day 1 up to 1 year Apparent Steady-state Volume of Distribution (Vss) of Loncastuximab Tesirine and SG3199 in Serum Day 1 up to 1 year Number of Participants Who Experience a Clinically Significant Change from Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status Baseline up to approximately 1 year Time to Cmax (Tmax) of Loncastuximab Tesirine and SG3199 in Serum Day 1 up to 1 year Number of Participants Who Experience an Adverse Event (AE) Up to approximately 3 years Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Interruption Up to approximately 1 year Area Under the Concentration-time Curve from Time Zero to Infinity (AUCinf) of Loncastuximab Tesirine and SG3199 in Serum Day 1 up to 1 year Number of Participants Who Experience a Clinically Significant Change from Baseline in Safety Laboratory Values Baseline up to approximately 1 year Duration of Response (DOR) Up to approximately 3 years Overall Survival (OS) Up to approximately 3 years Number of Participants Who Experience an Adverse Event (AE) Leading to Dose Delay Up to approximately 1 year Overall Response Rate (ORR) Up to approximately 3 years Complete Response (CR) Rate Up to approximately 3 years Progression-Free Survival (PFS) Up to approximately 3 years Relapse-Free Survival (RFS) Up to approximately 3 years
Trial Locations
- Locations (14)
Hospital Sírio-Libanês - Brasília
🇧🇷Brasília, Brazil
Hospital Sírio-Libanês - São Paulo
🇧🇷São Paulo, Brazil
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Daegu Gwang'yeogsi, Korea, Republic of
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
A Beneficência Portuguesa de São Paulo - Unidade Mirant
🇧🇷São Paulo, Brazil
Hospital 9 de Julho
🇧🇷São Paulo, Brazil
Korea University Anam Hospital
🇰🇷Seoul, Seongbuk District, Korea, Republic of
Dong-A University Hospital
🇰🇷Busan, Gyeongsangnam-do, Korea, Republic of
Hospital Mãe de Deus - Centro Integrado de Oncologia
🇧🇷Porto Alegre, Brazil
The Oncology Institute of Hope & Innovation - Lynwood
🇺🇸Lynwood, California, United States
Albert Einstein Israelite Hospital
🇧🇷São Paulo, Brazil
Severance Hospital
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Seoul Teugbyeolsi [Seoul-T'ukpyolshi], Korea, Republic of
Koo Foundation Sun Yat-Sen Cancer Center
🇨🇳Taipei, Taiwan