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Official Title

A Phase 2, Open-label, Study Evaluating Safety and Efficacy of the Loncastuximab in Relapsed/Refractory Marginal Zone Lymphoma

Phase
Phase 2
Sponsor
University of Miami
Enrollment
50
Timeline
Jun 2022 → Jun 2029
About This Study

The purpose of this research study is to see if loncastuximab tesirine has any benefits at dose levels researchers found acceptable in earlier studies in patients with related forms of immune cell cancers. The researchers want to find out the effects (good and bad) that loncastuximab tesirine has on the participant and the participant's condition.

Eligibility Criteria

Inclusion Criteria

  • 1Men and women, aged 18 years or older.
  • 2Histologically confirmed MZL, including extranodal, nodal, and splenic subtypes.
  • 3Previously received 1 or more lines of systemic therapy, including at least 1 anti-CD20 antibody (cluster of differentiation antigen 20) (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.
  • 4Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures \> 1.5 cm in the LDi and ≥ 1.0 cm in the longest perpendicular diameter as assessed by CT or MRI per response criteria for lymphomas.68 Imaging must be conducted within 6 weeks prior to the start of therapy.
  • 5Subjects 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.
  • 6Subjects with skin EMZL (extranodal marginal zone lymphoma) 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 \>1cm in diameter on the body that cannot be incorporated in one radiation field and at least one of them is histologically confirmed as MZL.
  • 7Subjects 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.
  • 8Subjects 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 5cm 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.
  • 9Subjects 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.
  • 10a. 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.
  • 11Patient should have at least one of the following criteria for treatment initiation):
  • 12Involvement of ≥3 nodal sites, each with diameter of ≥3 cm
  • 13Any nodal or extranodal tumor mass with a diameter of ≥5 cm
  • 14B 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.
  • 15Risk of local compressive symptoms that may result in organ compromise
  • 16Splenomegaly or splenic lesion without splenomegaly
  • 17Leukopenia attributed to MZL (leukocytes \< 1000/mm3)
  • 18Leukemia (\> 5.000 lymphoma cells/mm3)
  • 19Threatened organ function, especially for extranodal MZL
  • 20Requirement for transfusion or growth factor support attributed to lymphoma
  • 21Involvement of 2 or more extranodal sites, with tumor/lesion in each extranodal site ≥1 cm
  • 22Progression or relapsed within 24 months after MZL diagnosis in patients previously treated with ≥1 line of systemic therapy
  • 23Life expectancy \> 3 months.
  • 24ECOG (Eastern Cooperative Oncology Group ) performance status 0 to 2 (Refer to Appendix A).69
  • 25Adequate hematologic, hepatic, and renal function tested within 6 weeks prior to the start of therapy (values must not be achieved with growth factors):
  • 26ANC (absolute neutrophil count ) ≥ 1.0 × 109/L.
  • 27Hemoglobin ≥ 8.0 g/dL.
  • 28Platelet count ≥ 50 × 109/L.
  • 29Total bilirubin ≤ 1.5 × ULN (upper limit of normal ). Subjects with documented history of Gilbert's syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible.
  • 30ALT(alanine aminotransferase) /AST (aspartate aminotransferase ) ≤ 3.0 ULN or ≤ 5 × ULN in the presence of liver involvement by lymphoma.
  • 31Calculated creatinine clearance ≥ 45 mL/min by the Cockcroft-Gault Equation70 or the estimated glomerular filtration rate ≥ 45 mL/min/1.73 m2 using the Modification of Diet in Renal Disease formula.
  • 32Willingness to avoid pregnancy or fathering children based on the criteria below:
  • 33Woman 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).
  • 34Woman 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.
  • 35Man, 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

  • 1Evidence of DLBCL transformation. a. 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.
  • 2History of central nervous system lymphoma (either primary or metastatic) or leptomeningeal disease.
  • 3Concurrent anticancer therapy (eg, chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization).
  • 4Allogeneic 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.
  • 5Active graft versus host disease.
  • 6Receipt of anticancer medications or investigational drugs within the following intervals before the date of the first dose of study treatment:
  • 7\< 10 weeks from completion of any radio- or toxin-immunoconjugates.
  • 8\< 4 weeks for immunotherapy
  • 9\<. 3 weeks for radiotherapy.
  • 10\< 2 weeks for any investigational agent or other anticancer medications.
  • 11Steroids 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.
  • 12Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
  • 13Prior treatment-related toxicities have not resolved to NCI CTCAE v5.071 ≤ 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).
  • 14Previous treatment with anti CD19 (cluster of differentiation antigen 19 ) approaches
  • 15Current 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.
  • 16Significant concurrent, uncontrolled medical condition, including, but not limited to, renal, hepatic, hematological, 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.
  • 17Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment or exposure to a live vaccine within 30 days of dosing.
  • 18Known HIV infection or positivity on immunoassay. Note: HIV screening test is optional
  • 19Liver disease: HBV (hepatitis B virus) or HCV (hepatitis C virus) infection: Subjects positive for 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-RNA.
  • 20Current New York Heart Association Class II to IV congestive heart failure or uncontrolled arrhythmia.
  • 21Uncontrolled or symptomatic arrhythmia, stroke in last 6 months, liver cirrhosis, and autoimmune disorder requiring immunosuppression or long-term corticosteroids (\>10 mg daily prednisone equivalent)
  • 22Currently pregnant or breastfeeding.
  • 23Any 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.
  • 24Patients with impaired decision-making capacity

Locations

4 sites participating in this study

Emory University

Atlanta, Georgia 30322

Recruiting

Jean L Koff, MD

City of Hope National Medical Center

Duarte, California 91010

Recruiting

Geoffrey Shouse, DO, PhD

University of Miami

Miami, Florida 33136

Recruiting

Izidore Lossos, MD

Data sourced from ClinicalTrials.govView on ClinicalTrials.gov →