Loncastuximab Tesirine for the Treatment of Relapsed or Refractory Marginal Zone Lymphoma
Loncastuximab Tesirine for the Treatment of Relapsed or Refractory Marginal Zone Lymphoma
This phase II trial tests whether loncastuximab tesirine works to shrink tumors in patients with marginal zone lymphoma (MZL), a type of immune cell cancer, that has come back (relapsed) or become unresponsive to one or more treatments (refractory). Loncastuximab tesirine is composed of an antibody, called loncastuximab linked to a chemotherapy drug called tesirine. Loncastuximab attaches to specific proteins in the cancer cell and delivers tesirine only to the cancer cells because of this antibody. Ultimately this results in cancer cell death only without exposing normal cells to the tesirine.
Not Available
Phase II
Adults
Not Available
Not Available
Oluwole, Olalekan
National
Vanderbilt University
06-12-2025
Eligibility
18 Years
BOTH
NO
Inclusion Criteria:
Men and women, aged 18 years or older
Histologically confirmed MZL, including extranodal, nodal, and splenic subtypes
Previously received 1 or more lines of systemic therapy, including at least 1 anti-CD20 antibody (either as monotherapy or in combination as chemoimmunotherapy), with documented progression or documented failure to achieve CR or PR after the most recent systemic treatment regimen. Subjects with H. pylori-positive gastric extranodal MZL who received an initial treatment with currently accepted antibiotics may be considered eligible if, after antibiotic regimen, subject has histologically confirmed MZL and was subsequently treated with at least 1 line of systemic therapy
Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of >= 1 lesion that measures > 1.5 cm in the longest transverse diameter of a lesion [LDi] and >= 1.0 cm in the longest perpendicular diameter as assessed by computed tomography (CT) or magnetic resonance imaging (MRI) per response criteria for lymphomas. Imaging must be conducted within 6 weeks prior to the start of therapy * Subjects with splenic MZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that bone marrow infiltration of MZL is histologically confirmed * Subjects with skin extranodal marginal zone lymphoma (EMZL) who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that skin lesion measures >= 1.5 cm in diameter by tape measure and is documented by photo or there are multiple skin lesions measuring > 1 cm in diameter on the body that cannot be incorporated in one radiation field and at least one of them is histologically confirmed as MZL * Subjects with gastric extranodal MZL histologically confirmed and need therapy but do not have measurable disease and in which response to treatment can be assess by multiple random gastric biopsies * Subjects with conjunctival EMZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that conjunctival lesion measures >= 1 cm in diameter by tape measure and is documented by photo or there are multiple conjunctival lesions measuring together >1 5 cm that cannot be treated by radiation because of previous radiation therapy, contraindications to radiation and patient refusal to receive radiation therapy. At least one of these lesions needs be histologically confirmed as MZL
Subjects must be willing to provide a lymph node or tissue biopsy from the most recent available archival tissue or undergo an incisional or excisional lymph node or tissue biopsy. * Subjects with splenic MZL who do not have a tumor to biopsy or an archival tumor tissue sample are eligible for participation provided subject is willing to undergo a bone marrow biopsy or provide an archival bone marrow biopsy that was obtained before the date of the first dose of study treatment; bone marrow sample must show histologically confirmed infiltration of MZL
Patient should have at least one of the following criteria for treatment initiation): * Involvement of >= 3 nodal sites, each with diameter of >= 3 cm * Any nodal or extranodal tumor mass with a diameter of >= 5 cm * B symptoms (fever >= 38 degrees celsius of unclear etiology, night sweats, weight loss > 10% within the prior 6 months) or other symptoms attributed to disease or specific organ involvement associated with the relapse * Risk of local compressive symptoms that may result in organ compromise * Splenomegaly or splenic lesion without splenomegaly * Leukopenia attributed to MZL (leukocytes 1000/mm^3) * Leukemia (> 5.000 lymphoma cells/mm^3) * Threatened organ function, especially for extranodal MZL * Requirement for transfusion or growth factor support attributed to lymphoma * Involvement of 2 or more extranodal sites, with tumor/lesion in each extranodal site >= 1 cm * Progression or relapsed within 24 months after MZL diagnosis in patients previously treated with >= 1 line of systemic therapy
Life expectancy > 3 months
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
Absolute neutrophil count (ANC) >= 1.0 x 10^9/L (within 6 weeks prior to the start of therapy)
Hemoglobin >= 8.0 g/dL (within 6 weeks prior to the start of therapy)
Platelet count >= 50 10^9/L (within 6 weeks prior to the start of therapy)
Total bilirubin = 1.5 x upper limit of normal (ULN) (within 6 weeks prior to the start of therapy). Subjects with documented history of Gilberts syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible
Aspartate aminotransferase/alanine aminotransferase (AST/ALT) = 3.0 ULN or = 5 x ULN in the presence of liver involvement by lymphoma (within 6 weeks prior to the start of therapy)
Calculated creatinine clearance >= 45 mL/min by the Cockcroft-Gault Equation or the estimated glomerular filtration rate >= 45 mL/min/1.73 m^2 using the Modification of Diet in Renal Disease formula (within 6 weeks prior to the start of therapy)
Willingness to avoid pregnancy or fathering children based on the criteria below: * Woman of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR >= 12 months of amenorrhea and at least 45 years of age) * Woman of childbearing potential who has a negative serum pregnancy test at screening and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up at least 9 months after the last dose of loncastuximab tesirine. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed
Man, who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through at least 6 months after the last dose of study treatment. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed
Exclusion Criteria:
Evidence of diffuse large B-cell lymphoma (DLBCL) transformation * Subjects with presumptive evidence of transformation based on clinical assessment of factors such as, but not limited to, increasing lactate dehydrogenase, rapidly worsening disease, or frequent B-symptoms, must be ruled out for a transformation to a more aggressive disease, such as DLBCL
History of central nervous system lymphoma (either primary or metastatic) or leptomeningeal disease
Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization)
Allogeneic stem cell transplant within the last 6 months, or autologous stem cell transplant within the last 3 months before the date of the first dose of study treatment
Active graft versus host disease
Receipt of anticancer medications or investigational drugs within the following intervals before the date of the first dose of study treatment: * 10 weeks from completion of any radio- or toxin-immunoconjugates * 4 weeks for immunotherapy * 3 weeks for radiotherapy * 2 weeks for any investigational agent or other anticancer medications * Steroids that are used for treatment of allergy or other underlying condition are permittable, but not steroids started to treat lymphoma. Subjects receiving corticosteroids must be at a dose level = 10 mg/day within 7 days of the study treatment administration
Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy
Prior treatment-related toxicities have not resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 = grade 1 before the date of the first dose of study treatment, except for stable chronic toxicities (= grade 2) not expected to resolve (eg, stable grade 2 peripheral neurotoxicity)
Previous treatment with anti CD19 approaches
Current or previous other malignancy within 3 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy
Significant concurrent, uncontrolled medical condition, including, but not limited to, renal, hepatic, hematological, gastrointestinal (GI), endocrine, pulmonary, neurological, cerebral, or psychiatric disease. Patients with pleural effusion, pericardial effusion or ascites should not be enrolled in this study, unless effusions are caused by lymphoma
Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment or exposure to a live vaccine within 30 days of dosing
Known human immunodeficiency virus (HIV) infection or positivity on immunoassay * Note: HIV screening test is optional
Liver disease: hepatitis B virus (HBV) or hepatitis C virus (HCV) infection: Subjects positive for hepatitis B virus surface antigen (HBsAg) or hepatitis B core antibody will be eligible if they are negative for HBV-DNA; these subjects should be considered for prophylactic antiviral therapy. Subjects positive for anti-HCV antibody will be eligible if they are negative for HCV-ribonucleic acid (RNA)
Current New York Heart Association Class II to IV congestive heart failure or uncontrolled arrhythmia
Uncontrolled or symptomatic arrhythmia, stroke in last 6 months, liver cirrhosis, and autoimmune disorder requiring immunosuppression or long-term corticosteroids (> 10 mg daily prednisone equivalent)
Currently pregnant or breastfeeding
Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data
Patients with impaired decision-making capacity
Men and women, aged 18 years or older
Histologically confirmed MZL, including extranodal, nodal, and splenic subtypes
Previously received 1 or more lines of systemic therapy, including at least 1 anti-CD20 antibody (either as monotherapy or in combination as chemoimmunotherapy), with documented progression or documented failure to achieve CR or PR after the most recent systemic treatment regimen. Subjects with H. pylori-positive gastric extranodal MZL who received an initial treatment with currently accepted antibiotics may be considered eligible if, after antibiotic regimen, subject has histologically confirmed MZL and was subsequently treated with at least 1 line of systemic therapy
Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of >= 1 lesion that measures > 1.5 cm in the longest transverse diameter of a lesion [LDi] and >= 1.0 cm in the longest perpendicular diameter as assessed by computed tomography (CT) or magnetic resonance imaging (MRI) per response criteria for lymphomas. Imaging must be conducted within 6 weeks prior to the start of therapy * Subjects with splenic MZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that bone marrow infiltration of MZL is histologically confirmed * Subjects with skin extranodal marginal zone lymphoma (EMZL) who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that skin lesion measures >= 1.5 cm in diameter by tape measure and is documented by photo or there are multiple skin lesions measuring > 1 cm in diameter on the body that cannot be incorporated in one radiation field and at least one of them is histologically confirmed as MZL * Subjects with gastric extranodal MZL histologically confirmed and need therapy but do not have measurable disease and in which response to treatment can be assess by multiple random gastric biopsies * Subjects with conjunctival EMZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that conjunctival lesion measures >= 1 cm in diameter by tape measure and is documented by photo or there are multiple conjunctival lesions measuring together >1 5 cm that cannot be treated by radiation because of previous radiation therapy, contraindications to radiation and patient refusal to receive radiation therapy. At least one of these lesions needs be histologically confirmed as MZL
Subjects must be willing to provide a lymph node or tissue biopsy from the most recent available archival tissue or undergo an incisional or excisional lymph node or tissue biopsy. * Subjects with splenic MZL who do not have a tumor to biopsy or an archival tumor tissue sample are eligible for participation provided subject is willing to undergo a bone marrow biopsy or provide an archival bone marrow biopsy that was obtained before the date of the first dose of study treatment; bone marrow sample must show histologically confirmed infiltration of MZL
Patient should have at least one of the following criteria for treatment initiation): * Involvement of >= 3 nodal sites, each with diameter of >= 3 cm * Any nodal or extranodal tumor mass with a diameter of >= 5 cm * B symptoms (fever >= 38 degrees celsius of unclear etiology, night sweats, weight loss > 10% within the prior 6 months) or other symptoms attributed to disease or specific organ involvement associated with the relapse * Risk of local compressive symptoms that may result in organ compromise * Splenomegaly or splenic lesion without splenomegaly * Leukopenia attributed to MZL (leukocytes 1000/mm^3) * Leukemia (> 5.000 lymphoma cells/mm^3) * Threatened organ function, especially for extranodal MZL * Requirement for transfusion or growth factor support attributed to lymphoma * Involvement of 2 or more extranodal sites, with tumor/lesion in each extranodal site >= 1 cm * Progression or relapsed within 24 months after MZL diagnosis in patients previously treated with >= 1 line of systemic therapy
Life expectancy > 3 months
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
Absolute neutrophil count (ANC) >= 1.0 x 10^9/L (within 6 weeks prior to the start of therapy)
Hemoglobin >= 8.0 g/dL (within 6 weeks prior to the start of therapy)
Platelet count >= 50 10^9/L (within 6 weeks prior to the start of therapy)
Total bilirubin = 1.5 x upper limit of normal (ULN) (within 6 weeks prior to the start of therapy). Subjects with documented history of Gilberts syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible
Aspartate aminotransferase/alanine aminotransferase (AST/ALT) = 3.0 ULN or = 5 x ULN in the presence of liver involvement by lymphoma (within 6 weeks prior to the start of therapy)
Calculated creatinine clearance >= 45 mL/min by the Cockcroft-Gault Equation or the estimated glomerular filtration rate >= 45 mL/min/1.73 m^2 using the Modification of Diet in Renal Disease formula (within 6 weeks prior to the start of therapy)
Willingness to avoid pregnancy or fathering children based on the criteria below: * Woman of nonchildbearing potential (ie, surgically sterile with a hysterectomy and/or bilateral oophorectomy OR >= 12 months of amenorrhea and at least 45 years of age) * Woman of childbearing potential who has a negative serum pregnancy test at screening and who agrees to take appropriate precautions to avoid pregnancy (with at least 99% certainty) from screening through safety follow-up at least 9 months after the last dose of loncastuximab tesirine. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed
Man, who agrees to take appropriate precautions to avoid fathering children (with at least 99% certainty) from screening through at least 6 months after the last dose of study treatment. Permitted methods that are at least 99% effective in preventing pregnancy should be communicated to the subject and their understanding confirmed
Exclusion Criteria:
Evidence of diffuse large B-cell lymphoma (DLBCL) transformation * Subjects with presumptive evidence of transformation based on clinical assessment of factors such as, but not limited to, increasing lactate dehydrogenase, rapidly worsening disease, or frequent B-symptoms, must be ruled out for a transformation to a more aggressive disease, such as DLBCL
History of central nervous system lymphoma (either primary or metastatic) or leptomeningeal disease
Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization)
Allogeneic stem cell transplant within the last 6 months, or autologous stem cell transplant within the last 3 months before the date of the first dose of study treatment
Active graft versus host disease
Receipt of anticancer medications or investigational drugs within the following intervals before the date of the first dose of study treatment: * 10 weeks from completion of any radio- or toxin-immunoconjugates * 4 weeks for immunotherapy * 3 weeks for radiotherapy * 2 weeks for any investigational agent or other anticancer medications * Steroids that are used for treatment of allergy or other underlying condition are permittable, but not steroids started to treat lymphoma. Subjects receiving corticosteroids must be at a dose level = 10 mg/day within 7 days of the study treatment administration
Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy
Prior treatment-related toxicities have not resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 = grade 1 before the date of the first dose of study treatment, except for stable chronic toxicities (= grade 2) not expected to resolve (eg, stable grade 2 peripheral neurotoxicity)
Previous treatment with anti CD19 approaches
Current or previous other malignancy within 3 years of study entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy
Significant concurrent, uncontrolled medical condition, including, but not limited to, renal, hepatic, hematological, gastrointestinal (GI), endocrine, pulmonary, neurological, cerebral, or psychiatric disease. Patients with pleural effusion, pericardial effusion or ascites should not be enrolled in this study, unless effusions are caused by lymphoma
Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment or exposure to a live vaccine within 30 days of dosing
Known human immunodeficiency virus (HIV) infection or positivity on immunoassay * Note: HIV screening test is optional
Liver disease: hepatitis B virus (HBV) or hepatitis C virus (HCV) infection: Subjects positive for hepatitis B virus surface antigen (HBsAg) or hepatitis B core antibody will be eligible if they are negative for HBV-DNA; these subjects should be considered for prophylactic antiviral therapy. Subjects positive for anti-HCV antibody will be eligible if they are negative for HCV-ribonucleic acid (RNA)
Current New York Heart Association Class II to IV congestive heart failure or uncontrolled arrhythmia
Uncontrolled or symptomatic arrhythmia, stroke in last 6 months, liver cirrhosis, and autoimmune disorder requiring immunosuppression or long-term corticosteroids (> 10 mg daily prednisone equivalent)
Currently pregnant or breastfeeding
Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study treatment and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data
Patients with impaired decision-making capacity
