PACIFIC: Primary Mediastinal Large B-cell Lymphoma Treated With Antibody Therapy, Checkpoint Inhibitor in Frontline With ImmunoChemotherapy
- Conditions
- Ann Arbor Stage I Primary Mediastinal (Thymic) Large B-Cell LymphomaAnn Arbor Stage II Primary Mediastinal (Thymic) Large B-Cell LymphomaAnn Arbor Stage III Primary Mediastinal (Thymic) Large B-Cell LymphomaAnn Arbor Stage IV Primary Mediastinal (Thymic) Large B-Cell Lymphoma
- Registration Number
- NCT04745949
- Lead Sponsor
- M.D. Anderson Cancer Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 40
Inclusion Criteria:<br><br> - Histopathologically confirmed diagnosis of PMBL<br><br> - Require a CD30 expression level of 1% or greater in the tumor or<br> tumor-infiltrating lymphocytes by local immunohistochemistry<br><br> - No prior treatment except<br><br> - A prior limited-field radiotherapy<br><br> - A short course (up to 7 days) of glucocorticoids =< 100 mg daily of prednisone<br> equivalent which must cease prior to day 1 of cycle 1<br><br> - Stage of patients: Stages II, III, IV, and stage I >= 5 cm in the greatest dimension<br><br> - Patient or durable power of attorney (DPA) for healthcare must be able to understand<br> and voluntarily sign an Institutional Review Board (IRB)-approved informed consent<br> form<br><br> - Age >= 18 years at the time of signing the informed consent<br><br> - Patients must have bi-dimensional measurable disease, as defined as radiographically<br> apparent disease with the longest dimension of >= 1.5 cm<br><br> - Patients with performance status of =< 3 (3 only allowed if decline in status is<br> deemed related to lymphoma and felt potentially reversible by the treating<br> physician)<br><br> - Serum bilirubin < 1.5 x ULN except in patients with Gilbert's syndrome as defined by<br> > 80% unconjugated bilirubin<br><br> - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])<br> and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =<<br> 3 x ULN or < 5 x ULN if hepatic metastases are present<br><br> - Absolute neutrophil count (ANC) > 1000/mm^3 unless deemed related to lymphoma<br> involvement in the bone marrow and felt potentially reversible by the treating<br> physician<br><br> - Platelets > 1000/mm^3 unless deemed related to lymphoma involvement in the bone<br> marrow and felt potentially reversible by the treating physician<br><br> - Calculated creatinine clearance >= 30 ml/min by Cockcroft-Gault formula<br><br> - Patients must be willing to receive transfusions of blood products<br><br> - Women of childbearing potential must have a negative serum (beta-human chorionic<br> gonadotropin [beta-hCG]) at screening<br><br> - Women of childbearing potential and men who are sexually active with a woman of<br> childbearing potential must be practicing a highly effective method of birth control<br> during and after the study (12 months for women and 3 months for men), consistent<br> with local regulations regarding the use of birth control methods for subjects<br> participating in this clinical study. Men must agree to not donate sperm during and<br> for up to 3 months after their conclusion of therapy on study. For females, these<br> restrictions apply for 1 month after the last dose of study drug<br><br>Exclusion Criteria:<br><br> - Patients with an urgent need for cytoreductive treatment will be excluded<br><br> - Any serious medical condition including but not limited to uncontrolled<br> hypertension, uncontrolled congestive heart failure within past 6 months prior to<br> screening (class 3 [moderate] or class 4 [severe] cardiac disease as defined by the<br> New York Heart Association Functional Classification), uncontrolled diabetes<br> mellitus, active/symptomatic coronary artery disease, chronic obstructive pulmonary<br> disease (COPD), left ventricular ejection fraction (LVEF) less than 40%, renal<br> failure, active infection, history of invasive fungal infection, moderate to severe<br> hepatic disease (Child Pugh class B or C), active hemorrhage, laboratory<br> abnormality, or psychiatric illness that, in the investigators opinion places the<br> patient at unacceptable risk and would prevent the subject from signing the informed<br> consent form. Patients with history of cardiac arrhythmias should have cardiac<br> evaluation and clearance<br><br> - Previous anthracycline exposure with expected lifetime exposure to doxorubicin > 450<br> mg/m^2, considering the planned anthracycline exposure in this study with potential<br> six cycles of R-CHP<br><br> - Pregnant or lactating females<br><br> - Known hypersensitivity to brentuximab vedotin, nivolumab, rituximab, doxorubicin,<br> cyclophosphamide, or prednisone<br><br> - Known human immunodeficiency virus (HIV) infection with active viremia<br><br> - Patient with known HIV infection can be included if undetectable viral load,<br> CD4 >= 300 cells/microL and on HAART (highly active antiretroviral therapy)<br><br> - Patients with active viremia of hepatitis B infection<br><br> - Not including patients with prior hepatitis B vaccination; or positive serum<br> hepatitis B antibody<br><br> - Patients with active viremia of hepatitis C infection<br><br> - Known hepatitis C infection is allowed as long as there is no active disease<br> and is cleared by gastrointestinal (GI) consultation<br><br> - All patients with central nervous system involvement with lymphoma<br><br> - Diagnosis of prior malignancy within the past 2 years with the exception of<br> successfully treated basal cell carcinoma, squamous cell carcinoma of the skin,<br> carcinoma in situ of the cervix or breast. History of other malignancies are<br> allowed if in remission (including prostate cancer patients in remission from<br> radiation therapy, surgery or brachytherapy), not actively being treated, with a<br> life expectancy > 3 years<br><br> - Significant neuropathy (grades 2 or grade 1 with pain) within 14 days prior to<br> enrollment<br><br> - Contraindication to any of the required concomitant drugs or supportive treatments<br> or intolerance to hydration due to preexisting pulmonary or cardiac impairment<br> including pleural effusion requiring thoracentesis or ascites requiring paracentesis<br> not due to lymphoma<br><br> - Major surgery within 4 weeks of study entry or wound that is not healed from prior<br> surgery or trauma<br><br> - History of stroke or intracranial hemorrhage within 6 months prior to study entry<br><br> - Vaccinated with live, attenuated vaccines within 4 weeks of study entry
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Complete response rate
- Secondary Outcome Measures
Name Time Method Overall response rate (complete response + partial response);1-year progression-free survival;2 -year progression-free survival;1-year overall survival;2-year overall survival;Duration of response;Incidence of adverse events;Health-related quality of life