Safety and Antitumor Activity Study of Loncastuximab Tesirine and Durvalumab in Diffuse Large B-Cell, Mantle Cell, or Follicular Lymphoma
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03685344|
Recruitment Status : Terminated (In a limited number of patients, no additional activity was evident for the combination vs. Loncastuximab tesirine monotherapy.)
First Posted : September 26, 2018
Last Update Posted : April 29, 2021
|Condition or disease||Intervention/treatment||Phase|
|Diffuse Large B-Cell Lymphoma Mantle Cell Lymphoma Follicular Lymphoma||Drug: Loncastuximab Tesirine and Durvalumab||Phase 1 Phase 2|
This is a Phase 1b, open-label, single-arm combination study with a dose escalation phase (Part 1) followed by a dose expansion phase (Part 2). The study will enroll approximately 75 participants.
A standard 3+3 dose escalation design will be used for Part 1. The DLT period will be the 21 days after the first durvalumab dose.
Part 2 will consist of up to 3 expansion cohorts, one for DLBCL, one for MCL, and one for FL. Each cohort will be approximately 20 participants treated at the dose determined in Part 1.
The study will include a Screening Period (of up to 28 days), a Treatment Period (cycles of 3, 6, and 4 weeks), and a Follow-up Period (approximately every 12 week visits for up to 2 years after treatment discontinuation).
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Open-Label Study to Evaluate the Safety and Antitumor Activity of Loncastuximab Tesirine and Durvalumab in Patients With Advanced Diffuse Large B-Cell Lymphoma, Mantle Cell Lymphoma, or Follicular Lymphoma|
|Actual Study Start Date :||February 4, 2019|
|Actual Primary Completion Date :||October 27, 2020|
|Actual Study Completion Date :||October 27, 2020|
Dose escalation phase: Ascending doses of Loncastuximab tesirine will be administered using a traditional 3+3 design. Dose level 1: 90 µg/kg, every 3 weeks (Q3W). Dose level 2: 120 µg/kg, Q3W. Dose level 3: 150 µg/kg, Q3W. Loncastuximab tesirine will be given for 2 doses, 3 weeks apart.
Dose expansion phase: Loncastuximab tesirine will be administered at the recommended dose determined in the dose escalation phase. Durvalumab will also be administered at a dose of 1500 mg once every 4 weeks (Q4W) throughout the dose escalation phase and dose expansion phase.
Drug: Loncastuximab Tesirine and Durvalumab
- Number of Adverse Events (AEs) [ Time Frame: Day 1 until 30 days after the last dose of study drug ]An AE is defined as any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product, which does not necessarily have to have a casual relationship with this treatment.
- Number of Adverse Events of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Day 1 until 30 days after last dose of study drug ]Adverse events will be graded according to CTAE v4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5.
- Number of Serious Adverse Events (SAE) [ Time Frame: Day 1 to the end of follow-up period; maximum length of follow up is 2 years ]A SAE is defined as any AE that results in death, is life threatening, requires inpatient hospitalization of prolongation of existing hospitalization (hospitalization for elective procedures or for protocol compliance is not considered an SAE), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgement may jeopardize the patient or may require medical or surgical intervention to prevent any of the outcomes listed above.
- Number of SAEs of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or Above [ Time Frame: Day 1 to the end of follow-up period; maximum length of follow up is 2 years ]AEs will be graded according to CTCAE v.4.0 (or more recent). For events not included in the CTCAE criteria, the severity of the AE will be graded on a scale of 1 to 5.
- Number of dose limiting toxicities (DLTs) (dose escalation only) [ Time Frame: First 21-day cycle for each patient (dose escalation only) ]
- Number of Participants who Experience a Clinically Significant Change in Baseline in Laboratory Values [ Time Frame: Day 1 to end of trial; maximum of 3 years ]
- Number of Participants who Experience a Clinically Significant Change in Baseline in Vital Signs [ Time Frame: Day 1 to end of trial; maximum of 3 years ]
- Number of Participants who Experience a Clinically Significant Change in Baseline in Electrocardiogram (ECG) Results [ Time Frame: Day 1 to end of trial; maximum of 3 years ]
- Number of Particpants who Experience a Clinically Significant Change in Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Day 1 to end of trial; maximum of 3 years ]
- Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]ORR according to the 2014 Lugano classification, defined as the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR)
- Complete Response Rate (CRR) [ Time Frame: Up to 2 years ]Complete response rate defined as the percentage of treated participants with a BOR of CR
- Duration of response (DOR) [ Time Frame: Up to 3 years ]Time from first tumor response to disease progression or death
- Overall survival (OS) [ Time Frame: Up to 2 years ]Time between the start of treatment and death from any cause
- Relapse-Free Survival (RFS) [ Time Frame: Up to 2 years ]Time from the documentation of CR to disease progression or death
- Progression-Free Survival (PFS) [ Time Frame: Up to 2 years ]Time between start of treatment and the first documentation of progression, or death
- Maximum Observed Concentration (Cmax) of Loncastuximab Tesirine [ Time Frame: Cycle 3, Cycle 5, Cycle 6, and Cycle 7 (each cycle is 28 days) ]
- Time to Reach Maximum Concentration (Tmax) of Loncastuximab Tesirine [ Time Frame: Cycle 3, Cycle 5, Cycle 6, and Cycle 7 (each cycle is 28 days) ]
- Area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0 last) [ Time Frame: Cycle 3, Cycle 5, Cycle 6, and Cycle 7 (each cycle is 28 days) ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03685344
|United States, Alabama|
|University of Alabama at Birmingham|
|Birmingham, Alabama, United States, 35294|
|United States, Colorado|
|UCH-MHS Memorial Hospital Centeral|
|Colorado Springs, Colorado, United States, 80909|
|United States, Florida|
|University of Florida Health Shands Cancer Hospital|
|Gainesville, Florida, United States, 32603|
|University of Miami - Sylvester Comprehensive Cancer Center|
|Miami, Florida, United States, 33136|
|United States, New Jersey|
|Rutgers Cancer Institute of New Jersey|
|New Brunswick, New Jersey, United States, 08901|
|United States, New York|
|Icahm School of Medicine at Mount Sinai|
|New York, New York, United States, 10029|
|United States, Texas|
|Baylor University Medical Center|
|Dallas, Texas, United States, 75246|
|Joe Arrington Cancer Research and Treatment Center|
|Lubbock, Texas, United States, 79410|
|Baylor Scott & White Medical Center - Temple|
|Temple, Texas, United States, 76508|
|Hospital Clinic de Barcelona|
|Barcelona, Spain, 08036|
|Hospital General Universitario Gregorio Marañon Pabellón de Oncología|
|Madrid, Spain, 28009|
|Hospital Universitario Fundación Jiménez Díaz Unidad de Limfomas Servicio de Hematologia|
|Madrid, Spain, 28040|
|Hospital Universitario Virgen Macarena Servicio Oncologia Medica|
|Sevilla, Spain, 41009|
|Hospital Universitario Virgen Del Rocio|
|Sevilla, Spain, 41015|