El objetivo de este estudio es evaluar la eficacia de loncastuximab tesirina (ADCT-402) combinado con rituximab en comparación con la inmunoquimioterapia estándar.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Male or female participant aged 18 years or older
Pathologic diagnosis of DLBCL, as defined by the 2016 World Health Organization classification (including participants with DLBCL transformed from indolent lymphoma), or high-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 rearrangements
Relapsed (disease that has recurred following a response) or refractory (disease that failed to respond to prior therapy) disease following at least one multi-agent systemic treatment regimen \[For China only: Adequate first line anti-DLBCL therapy is defined as having received at least 4 cycles of multiagent systemic treatment regimen containing rituximab and anthracycline, unless the participants are intolerant to the regimen, or had disease progression during the treatment. If disease progression occurred during the treatment period, then the disease is considered refractory where the number of treatment cycles will not be specified. For participants who are ineligible for anthracycline, anthracycline is not required.\]
Not considered by the investigator to be a candidate for stem cell transplantation based on performance status, advanced age, and/or significant medical comorbidities such as organ dysfunction
Measurable disease as defined by the 2014 Lugano Classification as assessed by positron-emission tomography (PET)- computed tomography (CT) or by CT or magnetic resonance imaging (MRI) if tumor is not fluorodeoxyglucose (FDG)-avid on screening PET-CT
Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block (or minimum 10 freshly cut unstained slides if block is not available) Note: Any biopsy since initial diagnosis is acceptable, but if several samples are available, the most recent sample is preferred \[For China only: This inclusion criterion is not applicable\]
ECOG performance status 0-2
Adequate organ function as defined by screening laboratory values within the following parameters:
Absolute neutrophil count ≥1000/μL (off growth factors for at least 72 hours)
Platelet count ≥100000/μL without transfusion within the past 2 weeks
ALT, AST, and GGT ≤2.5 × the upper limit of normal (ULN)
Total bilirubin ≤1.5 × ULN (participants with known Gilbert's syndrome may have a total bilirubin up to ≤3 × 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.
Negative beta-human chorionic gonadotropin (β-hCG) pregnancy test within 7 days prior to start of study drug (Cycle 1 Day 1) for women of childbearing potential
Women of childbearing potential 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 giving informed consent until at least 7 months after the participant receives his last dose of study treatment.

Criterios de exclusión

Previous treatment with loncastuximab tesirine
Previous treatment with R-GemOx
Known history of hypersensitivity to a CD19 antibody, loncastumiximab tesirine (including SG3249) or any of its excipients, or history of positive serum human ADA to a CD19 antibody
Pathologic diagnosis of Burkitt lymphoma
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
Autologous transplant within 30 days prior to start of study drug (Cycle 1 Day 1)
Allogeneic transplant within 60 days prior to start of study drug (Cycle 1 Day 1)
Active graft-versus-host disease
Post-transplantation lymphoproliferative disorders
Active autoimmune disease, including motor neuropathy considered of autoimmune origin and other central nervous system (CNS) autoimmune disease
Human immunodeficiency virus (HIV) seropositive with any of the following:
CD4+ T-cell (CD4+) counts \<350 cells/μL
Acquired immunodeficiency syndrome-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 CNS involvement, 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)
Breastfeeding or pregnant
Uncontrolled hypertension (blood pressure ≥160/100 mm Hg repeatedly), unstable angina, congestive heart failure (greater than New York Heart Association class II), electrocardiographic evidence of acute ischemia, coronary angioplasty or myocardial infarction within 6 months prior to screening, uncontrolled atrial or ventricular cardiac arrhythmia, poorly controlled diabetes, severe chronic pulmonary disease, or other serious medical condition which is likely to significantly impair the participant's ability to tolerate the study treatment
Major surgery within 4 weeks prior to start of study drug (Cycle 1 Day 1); radiotherapy, chemotherapy or other antineoplastic therapy within 14 days prior to start of study drug (Cycle 1 Day 1), except shorter if approved by the Sponsor
Use of any other experimental medication within 14 days or 5 half-lives prior to start of study drug (Cycle 1 Day 1)
Received live vaccine within 4 weeks of Cycle 1 Day 1
Failure to recover to ≤Grade 1 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) from acute non-hematologic toxicity (except alopecia) due to previous therapy prior to screening
Congenital long QT syndrome or a corrected QTcF interval of ≥480 ms at screening (unless secondary to pacemaker or bundle branch block)
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
Known history of hypersensitivity to oxaliplatin or other platinum-based drugs, or gemcitabine, or rituximab, or any of their excipients

Ubicaciones

Clinica Adventista Belgrano

Belgrano, Buenos Aires, Argentina

Clínica de Nefrología, Urología y Enfermedades Cardiovasculares S.A.

Santa Fe, Buenos Aires, Argentina

Instituto Médico Especializado Alexander Fleming

Buenos Aires, Distrito Federal, Argentina

Grupo Gamma - Hospital Privado Rosario

Rosario, Santa Fe Province, Argentina

Estudio de fase 3, aleatorizado, de loncastuximab tesirina combinado con rituximab versus inmunoquimioterapia en pacientes con linfoma difuso de células B grandes (LDCBG) en recaída o refractario (LOTIS-5)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Loncastuximab Tesirine

Rituximab

Gemcitabine

Oxaliplatin

Ubicaciones

Clinica Adventista Belgrano

Clínica de Nefrología, Urología y Enfermedades Cardiovasculares S.A.

Instituto Médico Especializado Alexander Fleming

Grupo Gamma - Hospital Privado Rosario

Patrocinadores