[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"cns-lymphoma\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:cns-lymphoma":28},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,8,0,[8,42,64,92,131,153,177,198],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":26,"conditions":27,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":30,"lastUpdatePostDateStruct":31,"startDateStruct":34,"completionDateStruct":36,"leadSponsor":38,"locationsCount":41},"100526284","phase-1-90yy-ptt-endoradiotherapy-in-cns-lymphoma-patients-100526284",false,"NCT06132737","[90Y]Y-PTT Endoradiotherapy in CNS Lymphoma Patients","An Open-label Dose Escalation Study to Evaluate Safety, Tolerability, Biodistribution and Efficacy of [90Y]Y-PentixaTher for the Therapy of Recurrent or Refractory Primary or Isolated Secondary Central Nervous System Lymphoma.","Inclusion Criteria:\n\nPatients are eligible to be included in the study only if all of the following criteria apply and are maintained at Day -2 to Day 0 (before IMP infusion):\n\n1. Signed informed consent, by the patient or an authorized legal guardian in case the patient is temporarily not competent due to his or her disease, obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.\n2. Patients of either gender aged \\> 18 years.\n3. Body weight \\\u003C 180 kg.\n4. At least one measurable lymphoma manifestation in the CNS, either contrast-enhanced lesion in the brain parenchyma or measurable meningeal lesion.\n5. Histologically, cytologically or radiologically confirmed relapsed\u002Frefractory primary central nervous system lymphoma (PCNSL) or relapsed\u002Frefractory secondary central nervous system lymphoma (SCNSL). Initial histologic confirmation at first diagnosis is mandatory. No peripheral lymphoma evidence is allowed.\n6. Recurrent or refractory CNSL\n\n   1. For recurrent disease, comprising new lesions or recurrent CNSL after a complete response (CR) at that site, there are no maximum number of recurrences.\n   2. Refractory CNSL comprises patients with non-responding CNSL (no objective response rate (ORR), no progressive disease (PD)) to frontline therapy, or progressive disease after an initial, partial response (PR).\n7. Stored stem cells with at least ≥ 2 x 106 CD34+ cells\u002Fkg of body weight.\n8. If sexually active female patient of childbearing potential: patient agrees to take adequate contraceptive measures during study participation and agrees to continue use of this method for the duration of the study and for six months after the last dose.\n9. Female patient without childbearing potential: documented history (e.g., tubal ligation or hysterectomy) or is post-menopausal.\n10. For male patient whose partner is of child-bearing potential: patient is willing to ensure that he and his partner use effective contraception during the study and for six months after 90Y-PTT treatment.\n11. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.\n12. Confirmed presence of CXCR4 on technically evaluable tumor lesions documented by a visually CXCR4-positive \\[68Ga\\]Ga-PentixaFor positron emission tomography (PET) scan within two months prior to enrolment in the study or during Screening.\n13. Blood test results as follows:\n\n    1. Absolute neutrophil count: \\> 1.0 x 109\u002FL\n    2. Hemoglobin: ≥ 8 g\u002FdL\n    3. Platelets: ≥ 75 x 109\u002FL\n    4. Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP): ≤ 3 x ULN (upper limit of normal)\n    5. Serum creatinine: ≤ 2 x ULN and Cockcroft Gault calculated glomerular filtration rate (GFR) ≥ 50 mL\u002Fmin\n    6. Bilirubin: ≤ 3 x ULN\n\nExclusion Criteria:\n\nPatients are excluded from the study if any of the following criteria apply during screening or Day -2 to Day 0 (before IMP infusion):\n\n1. Known or suspected hypersensitivity to study product(s) or related products.\n2. Contraindication for contrast-enhanced magnetic resonance imaging (MRI) as set out in the relevant institutional guidelines (e.g., pacemaker, defibrillator, aneurysm clip, metal in the body, renal insufficiency, severe claustrophobia etc.) or contraindication for the use of gadolinium contrast for MRI.\n3. Previous participation in this study. Participation is defined as signed informed consent.\n4. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice). A pregnancy test will be performed at the start of the study for all female patients of childbearing potential (i.e., not surgically sterile or two years postmenopausal).\n5. Male of reproductive age who or whose partner(s) is not using an adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice).\n6. Participation in any clinical study of an approved or non-approved investigational medicinal product (IMP) within the last 30 days (or ≤ 5 terminal elimination half-lives of previous IMP, whichever is longer) before screening.\n7. Any disorder (e.g., active infection, unstable angina pectoris, cardiac arrhythmia (excluding atrial fibrillation and atrial flutter, uncontrolled congestive heart failure), poorly controlled hypertension, poorly controlled diabetes mellitus \\[HbA1c ≥ 9%\\], etc.) or laboratory findings, except for conditions associated with CNS lymphoma, which in the investigator's opinion might jeopardize patient's safety or compliance with the protocol.\n8. Presence of active infection, or history of serious infection six weeks prior to IMP administration. Patients with uncontrolled human immunodeficiency virus (HIV) infection as well as acute or chronic active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection are excluded (Note: Patients on antiretroviral therapy (ART) with controlled HIV infection (defined as sufficient ART compliance, non-measurable HIV and CD4+ T helper cells \\> 200\u002FMicro Liter) may be enrolled, if considered eligible for study treatment by the investigator.).\n9. SCNSL with systemic involvement.\n10. Chronic use (\\> 21 days) of immunosuppressive drugs, e.g., steroids for systemic autoimmune disease, due to previous organ transplantation, or other clinically evident form of immunodeficiency. Patients receiving only acute treatment (less than 21 days) with corticosteroids can be included.\n11. Any mental condition rendering the patient unable to understand the nature, scope, and possible consequences of the study, and\u002For evidence of an uncooperative attitude without designated legal representative.\n12. Brain radiation therapy ≤ 180 days before IMP infusion.","ALL","18 Years","120 Years",{"count":20,"type":21},15,"ESTIMATED","INTERVENTIONAL",[24,25],"PHASE1","PHASE2","This will be an open-label, single-arm, national phase 1\u002F2 therapeutic study to evaluate the safety, tolerability, and preliminary efficacy of \\[90Y\\]Y-PentixaTher (\\[90Y\\]Y-PTT) for the treatment of recurrent or refractory primary or isolated secondary central nervous system (CNS) lymphoma.\n\nThe study will be performed in three cohorts with different dose levels according to the best-of-5 dose escalation design. A safety review committee (SRC) will evaluate dose-limiting toxicities and decide about escalation and de-escalation.\n\nEligible patients will receive one cycle of \\[90Y\\]Y-PTT, which will be administered intravenously. There will be no comparator in this study.\n\nSafety, biodistribution, dosimetry and efficacy will be evaluated during the core study phase (Visit 1 until Visit 5). Thereafter three follow-up (FU) visits will take place, at three-months intervals to evaluate the extent of disease.",[28],"CNS Lymphoma","RECRUITING","2026-06-03",{"date":32,"type":33},"2026-06-05","ACTUAL",{"date":35,"type":33},"2023-11-07",{"date":37,"type":21},"2028-03-26",{"name":39,"class":40},"Pentixapharm AG","INDUSTRY",2,{"id":43,"slug":44,"hasResults":11,"nctId":45,"briefTitle":46,"officialTitle":46,"acronym":4,"eligibilityCriteria":47,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":48,"targetDuration":4,"studyType":22,"phases":50,"briefSummary":51,"conditions":52,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":53,"lastUpdatePostDateStruct":54,"startDateStruct":56,"completionDateStruct":58,"leadSponsor":60,"locationsCount":63},"100572228","phase-1-zanubrutinib-in-combination-with-pola-r-chp-and-high-dose-methotrexate-in-patients-with-secondary-cns-lymphoma-100572228","NCT06730542","Zanubrutinib in Combination With Pola-R-CHP and High-dose Methotrexate in Patients With Secondary CNS Lymphoma","Inclusion Criteria:\n\n1. Men and women ≥ 18 years of age on the day of signing the informed consent form (or the legal age of consent in the jurisdiction in which the study is taking place).\n2. Patients must have histologic confirmation of large B-cell lymphoma (LBCL) defined by the World Health Organization (WHO) classification. All LBCL subtypes are acceptable. Note: Patients with prior treatment for indolent lymphoma are still eligible for participation as long as they did not receive anthracycline-based therapy.\n3. Baseline 18-fluorodeoxyglucose (FDG)-positron emission tomography scan\u002Fcomputed tomography (PET\u002FCT) must demonstrate FDG avid lesions compatible with CT-defined anatomical tumor sites (Note: FDG-PET\u002FCT is not mandatory, and patients with CT scans only will be eligible for study entry as well). Patients should have at least 1 measurable site of disease per Lugano classification in FDG-PET\u002FCT or CT scans.\n4. Presence of systemic and CNS involvement (brain, cerebellum, brainstem, meninges, cranial nerves, eyes, spinal cord, or a combination of these) at presentation.\n5. Determination of CNS involvement can be by brain biopsy, cerebrospinal fluid (CSF) evaluation by cytology and\u002For flow cytometry, neuroimaging, or strong clinical suspicion by Investigator for which CNS targeted therapy is recommended (ie, numb chin syndrome in patients with high CNS involvement risk).\n6. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2, except due to lymphoma involvement.\n7. Life expectancy of greater than ≥ 3 months.\n8. Women should avoid becoming pregnant while taking zanubrutinib and for up to 90 days after ending treatment. Therefore, women of childbearing potential must use highly effective contraceptive measures while taking zanubrutininb and for up to 90 days after stopping treatment. It is currently unknown whether zanubrutinib may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should add a barrier method. Pregnancy testing is recommended for women of reproductive potential prior to initiating therapy.\n\n   Agreement to use contraception during study participation.\n   1. Female patients of childbearing potential must use highly effective methods of contraception. Recommended acceptable contraception methods are included in Section 5.12.\n   2. Patients using hormonal contraceptives (eg, birth control pills or devices) must use a barrier method of contraception (eg, condoms) as well.\n   3. A woman is considered of childbearing potential, ie, fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.\n   4. A post-menopausal state is defined as no menses for 12 months without an alternative medical cause.\n9. Male patients with a female partner of childbearing potential are eligible if they abstained, are vasectomized or if they agree to the use of barrier contraception with other methods described above during the study treatment period and for 90 days after the last dose of zanubrutinib.\n10. Patients must have normal organ and marrow function as defined below:\n\n    1. Absolute neutrophil count (ANC) \\> 1,000 cells\u002Fmm3 independent of growth factor support within 7 days of study entry (≥ 750 cells\u002Fmm3 if lymphoma involvement of the bone marrow or spleen).\n    2. Platelets ≥ 75,000 platelets\u002Fmm3 independent of transfusion support within 7 days of study entry (≥ 50,000\u002Fmm3 independent of transfusion support within 7 days of study entry if lymphoma involvement of the bone marrow or spleen).\n    3. Hemoglobin \\> 9 g\u002FdL or \\> 8 g\u002FdL in case of bone marrow involvement by lymphoma independent of transfusion support within 7 days of study entry.\n    4. Serum total bilirubin ≤ 2 x upper limit of normal (ULN; except patients with Gilberts syndrome).\n    5. Aspartate aminotransferase (AST; serum glutamic-oxaloacetic transaminase (SGOT)) and alanine transaminase (ALT); serum glutamic-pyruvic transaminase (SGPT)) ≤2.5 x institutional ULN (≤3x institutional ULN if lymphoma involvement of the liver).\n    6. Creatinine within normal institutional limits, or creatinine clearance ≥ 40 mL\u002Fmin (as estimated by the Cockcroft-Gault equation or alternative formula according to institutional guidelines) for patients with creatinine levels above institutional normal.\n11. Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments (SoA).\n\nExclusion Criteria:\n\n1. Primary CNS lymphoma without evidence of systemic lymphoma.\n2. Prior systemic lymphoma therapy (Note: 1 cycle of an anthracycline based regimen, such as rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (R-CHOP), polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP), dose-adjusted etoposide phosphate, prednisone, oncovin, cyclophosphamide, hydroxydaunorubicin, and rituximab (EPOCH-R), or rituximab, cyclophosphamide, vincristine, doxorubicin, and methotrexate (R-Codox-M), and\u002For 1 dose of intrathecal therapy, will be allowed before enrollment \\[Section 5.9\\]). Note: Patients with prior treatment for indolent lymphoma are still eligible for participation as long as they did not receive anthracycline-based therapy.\n3. Any uncontrolled or clinically significant cardiovascular disease including the following:\n\n   1. Myocardial infarction within 6 months before screening;\n   2. Unstable angina within 3 months before screening;\n   3. New York Heart Association class III or IV congestive heart failure;\n   4. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes).\n   5. Uncontrolled hypertension as indicated by ≥ 2 consecutive blood pressure measurements showing systolic blood pressure \\> 170 mm Hg and\u002For diastolic blood pressure \\> 105 mm Hg at screening.\n   6. QT interval corrected with Fridericia's formula (QTcF) \\> 450 msec or other significant electrocardiogram (EKG) abnormalities, including second-degree atrioventricular block Type II or third-degree atrioventricular block.\n4. Active and\u002For ongoing autoimmune anemia and\u002For autoimmune thrombocytopenia (eg, idiopathic thrombocytopenia purpura).\n5. Uncontrolled intercurrent illness such as liver cirrhosis, autoimmune disorder requiring immunosuppression or long-term corticosteroids (\\> 10 mg daily prednisone equivalent), or any other serious medical condition, laboratory abnormality, or psychiatric illness which would compromise ability to comply with study procedures.\n6. Severe or debilitating pulmonary disease.\n7. Concurrent malignancy requiring active therapy.\n8. Prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 prostate cancer.\n9. Active fungal, bacterial and\u002For viral infection requiring systemic therapy.\n10. Breastfeeding or pregnant women.\n11. Known active infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows:\n\n    1. Patients with positive HIV test and undetectable viral load will be eligible for this study.\n    2. Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible if hepatitis B virus (HBV) DNA is undetectable (\\\u003C 20 IU), and if they are willing to undergo monitoring every 4 weeks for HBV reactivation.\n    3. Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable. For more information regarding hepatitis B and C testing, please refer to Section 9.2.5.4.\n12. Patients with impaired decision-making capacity.\n13. Ongoing treatment with medications that are strong cytochrome P450 (CYP), family 3, subfamily A (CYP3A) inducers.\n14. Underlying medical conditions that, in the Investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs.\n15. Unable to swallow capsules or disease significantly affecting gastrointestinal function, such as malabsorption syndrome, stomach or small bowel resection, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.\n16. History of severe bleeding disorder, such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood transfusion or other medical intervention.\n17. History of stroke or intracranial hemorrhage within 180 days before the first dose of zanubrutinib.\n18. Major surgery within 4 weeks of the first dose of zanubrutinib. Major surgery is defined as open-heart, reconstructive, transplant, removal of a brain tumor or a damaged kidney surgery.\n19. The patient requires treatment with warfarin, warfarin derivatives, or other vitamin K antagonists.\n20. Vaccination or requirement for vaccination with a live vaccine within 28 days prior to the first dose of study drug or at any time during planned study treatment.\n21. Hypersensitivity to zanubrutinib, any components of pola-R-CHP, regimen, and\u002For high-dose (HD) methotrexate (MTX), or any of the other ingredients of the applicable study medications.\n22. Concurrent participation in another therapeutic clinical trial.",{"count":49,"type":21},20,[24],"The purpose of this study is to is to determine the effects (good and bad) of Zanubrutinib in Combination with Pola-R-CHP and High-dose Methotrexate in patients with Secondary Central Nervous System (CNS) Lymphoma.",[28],"2026-05-11",{"date":55,"type":33},"2026-05-14",{"date":57,"type":33},"2025-04-17",{"date":59,"type":21},"2030-04-30",{"name":61,"class":62},"Juan P. Alderuccio, MD","OTHER",1,{"id":65,"slug":66,"hasResults":11,"nctId":67,"briefTitle":68,"officialTitle":69,"acronym":4,"eligibilityCriteria":70,"healthyVolunteers":11,"sex":16,"minAge":71,"maxAge":4,"enrollmentInfo":72,"targetDuration":4,"studyType":22,"phases":74,"briefSummary":75,"conditions":76,"keywords":80,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":83,"lastUpdatePostDateStruct":84,"startDateStruct":86,"completionDateStruct":88,"leadSponsor":90,"locationsCount":63},"100446836","phase-1-preliminary-safety-and-tolerability-of-cd19x22-car-t-cells-in-adolescent-and-adult-rr-b-nhl-patients-100446836","NCT05098613","Preliminary Safety and Tolerability of CD19x22 CAR T Cells in Adolescent and Adult R\u002FR B-NHL Patients","Phase 1 Study of Bispecific CD19 and CD22 Chimeric Antigen Receptor Co-Expressing T Cells (CD19x22 CAR T) in Adolescent and Adult Patients With Relapsed and\u002For Refractory B-Non-Hodgkin's Lymphoma (B-NHL)","Inclusion Criteria:\n\n1\\. Age: ≥ 16 years of age with no upper age limit. (NOTE: the first three subjects on this trial must be ≥ 18 years of age.)\n\nCOHORT 1: Non-CNS B-NHL\n\n1. Histologically confirmed aggressive B-cell NHL including the following types defined by World Health Organization (WHO) 2008:\n\n   a. Diffuse Large B-Cell Lymphoma (DLBCL) not otherwise specified; T cell\u002Fhistiocyte rich large B cell lymphoma; DLBCL associated with chronic inflammation; Epstein Barr Virus (EBV)+ DLBCL of the elderly; OR b. Primary mediastinal (thymic) large B cell lymphoma; OR c. Transformation to DLBCL; OR d. High grade B-cell Lymphoma (HGBL).\n2. Subjects must not have any signs or symptoms of CNS disease or detectable evidence of CNS disease on magnetic resonance imaging (MRI) at screening; subjects who have been previously treated for CNS disease, but have no evidence of disease at screening are eligible for this cohort.\n3. Subjects must have disease progression confirmed by either flow cytometry or immunohistochemistry (IHC), disease stabilization, or disease recurrence after at least two lines of therapy.\n\n   a. The two lines of prior therapy must include an anthracycline and anti-CD20 monoclonal antibody treatment.\n\n   b. Relapse or refractory after single antigen targeting CAR T cell therapy\n4. Must have evaluable or measurable disease according to the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma; lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.\n\nCOHORT 2: MANTLE CELL LYMPHOMA (MCL)\n\n1. Mantle Cell Lymphoma (MCL).\n\n   a. Results of all tests conducted on the tissue at initial diagnosis and\u002For relapse, including, but not limited to, the MCL subtype (classic and blastoid), Ki-67 proliferation index, and TP53 mutation status should be provided if done.\n2. Subjects must have relapsed and\u002For refractory MCL confirmed by either flow cytometry or immunohistochemistry (ICH), disease stabilization, or disease recurrence after at least two lines of therapy including any combination of the agents below:\n\n   a. An anti-CD20-directed therapy b. A BTK inhibitor c. Anthracycline or Bendamustine d. Relapse or refractory after single antigen targeting CAR T cell therapy.\n3. Must have evaluable or measurable disease according to the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma; lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. MCL patients without measurable nodal or extranodal disease by IWG criteria are eligible if they have bone marrow involvement of MCL at relapse\n\nCOHORT 3: PRIMARY CNS LYMPHOMA OR SECONDARY CNS LYMPHOMA\n\n1. Subjects with relapsed and\u002For refractory primary CNS lymphoma (PCNSL) OR secondary CNS lymphoma (SCNSL), as defined by the following:\n\n   a. Absence of measurable disease outside the CNS, as determined by radiographic imaging (i.e. PET\u002FCT).\n\n   b. Detectable CNS disease, as defined as: i. At least 1 site of measurable disease within the brain or spinal cord that is ≥ 1 cm in the longest diameter based on MRI or PET\u002FCT imaging; OR, ii. Neoplastic B-cells detectable within the CSF or vitreous by flow cytometry or cytology.\n2. Subjects must have disease progression confirmed by either flow cytometry or immunohistochemistry (IHC), disease stabilization, or disease recurrence after at least one line of therapy.\n\nALL COHORTS:\n\n1. Subjects who have undergone autologous stem cell transplantation (SCT) with disease progression or relapse are eligible.\n2. Subjects who have undergone allogeneic SCT will be eligible if, in addition to meeting other eligibility criteria, are:\n\n   1. At least 100 days post-transplant,\n   2. Do not have active graft versus host disease (GVHD)\n3. Any standard of care systemic therapy prior to leukapheresis must follow the washout period.\n4. Any steroid use (dexamethasone or prednisone) prior to apheresis must follow the washout period. Physiological replacement doses are allowable with no washout period. Topical or inhaled steroids for localized GVHD is allowable.\n5. Peripheral blood CD3 count must be \\>0.15 x 10 (to the 6th) cells\u002FmL within 14 days prior to proceeding with apheresis.\n6. Toxicities from prior therapy must be stable and recovered to ≤ grade 1 (exceptions include non-clinically significant toxicities such as alopecia and the organ function definitions provided in inclusion criteria 12).\n7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or Karnofsky ≥ 80%.\n8. Adequate organ function as defined by:\n\n   1. Absolute neutrophil count (ANC) ≥ 500\u002FμL\n   2. Platelet count ≥ 50,000\u002F μL.\n   3. Renal: Creatinine ≤ 2 mg\u002FdL OR creatinine clearance (as estimated by Cockcroft Gault equation) ≥ 60 mL\u002Fmin.\n   4. Hepatic: Serum alanine aminotransferase (ALT)\u002Faspartate aminotransferase (AST) ≤ 3 upper limit of normal (ULN).\n   5. Total bilirubin ≤ 2 mg\u002Fdl, except in subjects with Gilbert's syndrome where a bilirubin \\\u003C4.0 will be acceptable.\n   6. Cardiac: Ejection fraction ≥ 40%, no evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings within 6 weeks of apheresis.\n   7. Pulmonary: No clinically significant pleural effusion and;\n\n   i. Baseline oxygen saturation must be \\> 92% on room air\n9. Females of childbearing potential must have a negative serum pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 6 months are not considered to be of childbearing potential).\n10. Subjects of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for 12 months after receiving the CD19x22 infusion; females of childbearing potential must have a negative pregnancy test.\n\n21\\. Must be able to give informed consent; subjects unable to give informed consent will not be eligible for this study.\n\n22\\. Be able to consent to long-term follow-up protocol (#20-0188).\n\nExclusion Criteria:\n\n1. Age \\\u003C 16 years of age.\n2. Patient who is intolerant of contrast-enhanced MRI due to allergic reactions to contrast agents. Only applicable to Cohort 3.\n3. History of other malignancies, unless they have been disease free for at least 3 years. Exceptions include non-melanoma skin cancer or carcinoma in situ and localized prostate cancer not on active treatment.\n4. Uncontrolled fungal, bacterial, viral, or other infection requiring antimicrobials for management; uncomplicated infections are permitted if responding to active treatment.\n5. Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (hepatitis B surface antigen \\[HBsAg\\] positive) or hepatitis C.\n6. History of known myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment or have cardiac atrial or cardiac ventricular lymphoma involvement.\n7. Venous thrombosis or embolism not managed on a stable regimen of anticoagulation.\n8. Any medical condition that in the judgement of the sponsor is likely to interfere with assessment of safety or efficacy of study treatment.\n9. History of severe immediate hypersensitivity reaction to any of the agents used in this study.\n10. Pregnancy (serum pregnancy test must be obtained at time of enrollment for females of childbearing potential and to be repeated 72 hours prior to lymphodepleting chemotherapy regimen); females who have undergone surgical sterilization or who have been postmenopausal for at least 6 months are not considered to be childbearing potential.\n11. Lactating.\n12. In the investigator's judgment, the subject is unlikely to complete all protocol required study visits or procedures, including follow up visits, or comply with the study requirements for participation.\n13. Unwilling to participate in long-term follow-up protocol that is required if CAR T cell therapy is administered at CU Anschutz.\n\nLYMPHODEPLETING CHEMOTHERAPY ELIGIILITY:\n\nIn order to proceed with lymphodepleting chemotherapy, enrolled participants must meet all eligibility criteria below within 72 hours prior to lymphodepletion, unless otherwise specified:\n\n* If the participant received bridging therapy after apheresis, confirmation of disease reevaluation is required. It must be within 6 weeks of initiation of LD chemotherapy.\n\n  * Confirmation that the participant has met the washout period for bridging therapy.\n* Negative serum pregnancy test (for women of childbearing potential)\n* Adequate organ function as defined by:\n\n  * Absolute neutrophil count (ANC) ≥ 500\u002FμL.\n  * Platelet count ≥ 50,000\u002F μL.\n  * Renal: Creatinine ≤ 2 mg\u002FdL OR creatinine clearance (as estimated by Cockcroft Gault equation) ≥ 60 mL\u002Fmin.\n  * Hepatic: Serum alanine aminotransferase (ALT)\u002Faspartate aminotransferase (AST) ≤ 3 upper limit of normal (ULN).\n  * Total bilirubin ≤ 2 mg\u002Fdl, except in subjects with Gilbert's syndrome where a bilirubin \\\u003C3.0 will be acceptable.\n  * Pulmonary: No clinically significant pleural effusion and; Baseline oxygen saturation must be \\> 92% on room air.\n  * Cardiac: Ejection fraction ≥ 45%, no evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO) (only if subject received bridging anthracycline or developed a significant illness prior to LD-chemo per investigator assessment.) If clinically indicated, ECHO must be performed within 2 weeks prior to LD-chemotherapy.\n\nCD19x22 CAR T CELL INFUSION ELIGIBILITY\n\nIn order to proceed with CD19x22 CAR T Cell Infusion, enrolled participants must meet all eligibility criteria below within 24 hours prior to CD19x22 CAR T Cell infusion, unless otherwise specified:\n\n* CD19x22 CAR T cells must have met manufacturing release criteria (unless prospectively approved by IND Sponsor, Gates Institute Medical Lead, and FDA).\n* Confirmation that the site has Anakinra and Ruxolitinib in stock and available (should IEC-HS treatment be required).\n* ECOG ≤2 or Karnofsky≥ 50%.\n* Clinically stable without evidence of vital sign instability, including the lack of supportive vasoactive drugs or intensive care unit support.\n* Oxygen saturation \\> 92% on room air; cannot be on supplemental oxygen.\n* No evidence of uncontrolled, significant tumor lysis syndrome prior to cell infusion per investigator assessment.\n* No evidence of rapidly progressive NHL per investigator determination.\n* Participants' temperature is \\\u003C38.0 °C within 48 hours prior to cell infusion. (If the source of fever cannot be identified \\[after thorough infectious disease work-up\\], and the suspected cause is underlying malignancy, discussion and approval by the Gates Institute Medical Lead may allow continued infusion of CD19x22 cells. This should be appropriately documented in the patient's medical record.\n* Liver transaminase (ALT and AST) \\\u003C 5 x institutional ULN (\\\u003C grade 3) based on age- and laboratory- specific normal ranges.\n* Adequate renal function as defined by creatinine ≤ 2 mg\u002FdL OR creatinine clearance (as estimated by the Cockcroft- Gault equation) ≥ 60 mL\u002Fmin.\n\nIf these criteria are not met, measures can be taken to resolve the underlying condition(s). If successful, cells may be infused up to (and including) 7 days following the time of the planned infusion with no additional lymphodepletion. If the CD19x22 CAR T Cell infusion is delayed more than 7 days, lymphodepleting chemotherapy MAY be repeated, per the investigator's discretion. Prior to commencing a second round of lymphodepletion, participants must meet lymphodepletion criteria described above.","16 Years",{"count":73,"type":21},68,[24],"This open-label, single arm phase 1 trial aims to determine the safety and tolerability of anti-CD19 and anti-CD22 chimeric antigen receptor-expressing (CAR) T cells (CD19x22 CAR T) in adolescents and adults with relapsed\u002Frefractory (R\u002FR) B-cell Non-Hodgkin Lymphoma (B-NHL). This trial will determine the maximum tolerated dose of CD19x22 CAR T cells using a standard 3+3 trial design.",[77,78,79,28],"Non-Hodgkin Lymphoma","B-cell Non-Hodgkin Lymphoma (B-NHL)","Mantle Cell Lymphoma (MCL)",[81,82],"Relapsed","Refractory","2025-12-17",{"date":85,"type":33},"2025-12-24",{"date":87,"type":33},"2021-12-21",{"date":89,"type":21},"2027-12",{"name":91,"class":62},"University of Colorado, Denver",{"id":93,"slug":94,"hasResults":11,"nctId":95,"briefTitle":96,"officialTitle":97,"acronym":98,"eligibilityCriteria":99,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":100,"targetDuration":4,"studyType":22,"phases":102,"briefSummary":103,"conditions":104,"keywords":118,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":122,"lastUpdatePostDateStruct":123,"startDateStruct":125,"completionDateStruct":127,"leadSponsor":129,"locationsCount":41},"100542472","phase-1-t-cell-therapy-eb103-in-adults-with-relapsedrefractory-b-cell-non-hodgkins-lymphoma-nhl-100542472","NCT06343311","T-Cell Therapy (EB103) in Adults With Relapsed\u002FRefractory B-Cell Non-Hodgkin's Lymphoma (NHL)","An Open-Label, Dose Escalation, Multi-Center Phase I\u002FII Clinical Trial of EB103 T-Cell Therapy in Adults With Relapsed\u002FRefractory (R\u002FR) B-Cell Non-Hodgkin's Lymphoma (NHL)","STARLIGHT-1","Inclusion Criteria:\n\n* Age 18 years or older at the time of informed consent\n* Histologically confirmed R\u002FR B-cell non-Hodgkin's lymphoma (NHL)\n* Adequate organ function\n* Relapsed or refractory (R\u002FR) disease defined as ONE OR MORE of the following:\n\n  * R\u002FR after ≥ 2 lines of systemic therapy\n\n    * For the following NHL types: Burkitt lymphoma, Precursor B-cell lymphoblastic lymphoma, or Mantle cell lymphoma: R\u002FR after ≥ 1 lines of systemic therapy\n  * Disease progression or recurrence ≤ 12 months after autologous hematopoietic stem cell transplantation (HSCT)\n  * For subjects who are considered transplant-ineligible: progressive disease as best response after ≥ 4 cycles of first-line therapy and stable disease as best response after ≥ 2 cycles of second-line (salvage) therapy; subject must have received an anti-CD20 monoclonal antibody and an anthracycline as one of their qualifying regimens\n* All subjects must have received an appropriate chemoimmunotherapy regimen which at a minimum includes an:\n\n  * Anti-CD20 monoclonal antibody AND\n  * An anthracycline-containing chemotherapy regimen\n* Positron emission tomography (PET)-positive disease according to Cheson 2014\n* Eastern Cooperative Oncology Group (ECOG) ≤ 2\n* Toxicities due to prior therapy must be stable and recovered to Grade 1 or less\n\nExclusion Criteria:\n\n* Prior CD19-targeted cellular therapy\n* History of Richter's transformation of chronic lymphocytic leukemia (CLL)\n* History of another primary malignancy that has not been in remission for ≥ 2 years.\n* History or presence of clinically relevant Central Nervous System (CNS) pathology\n* CNS disease which is progressing on most recent therapy or with a parenchymal mass which is likely to cause clinical symptoms\n* Subjects with active cardiac lymphoma involvement which is not responding to treatment\n* History of myocardial infarction, cardiac angioplasty and stenting, unstable angina, or other clinically significant cardiac disease within 6 months of informed consent\n* Active, uncontrolled systemic bacterial, fungal, or viral infection. Patients with HIV, hepatitis B, or hepatitis C are eligible provided their infection is being treated and the viral load is controlled.\n* History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression\u002Fsystemic disease modifying agents within the last 2 years\n* History of severe, immediate hypersensitivity reaction to any agents used in this study, including the conditioning chemotherapeutic agents\n* Venous thrombosis or embolism not managed on a stable regimen of anticoagulation\n* Autologous HSCT within 3 months of informed consent\n* Subjects with a prior allogeneic transplant at least 6 months prior to study enrollment are eligible unless experienced graft-versus-host disease (GvHD) that requires ongoing treatment with systemic steroids or other systemic GvHD therapy, such as a calcineurin inhibitor, within 12 weeks of initial screening\n* Live vaccine within 3 months prior to planned start of conditioning regimen",{"count":101,"type":21},21,[24,25],"This is an open-label, dose escalation, multi-center, Phase I\u002FII clinical trial to assess the safety of an autologous T-cell therapy (EB103) and to determine the Recommended Phase II Dose (RP2D) in adult subjects (≥ 18 years of age) who have relapsed\u002Frefractory (R\u002FR) B-cell NHL. The study will include a dose escalation phase followed by an expansion phase.",[105,106,107,77,108,109,110,111,112,113,114,115,28,116,117],"B-Cell Non-Hodgkin's Lymphoma (NHL)","Lymphoma, Non-Hodgkins","Lymphomas Non-Hodgkin's B-Cell","Non-Hodgkin's Lymphoma","Large B-Cell Lymphoma","Lymphoma, Non-Hodgkin's, Adult","Lymphoma","Refractory Non-Hodgkin Lymphoma","Relapsed Non-Hodgkin Lymphoma","Lymphoma, Non-Hodgkin","HIV Associated Lymphoma","High-grade B-cell Lymphoma","Refractory B-Cell Non-Hodgkin Lymphoma",[119,108,120,111,109,112,113,121,28,116,117],"B-Cell Non-Hodgkin's Lymphoma","NHL","HIV Lymphoma","2025-08-04",{"date":124,"type":33},"2025-08-07",{"date":126,"type":33},"2024-06-01",{"date":128,"type":21},"2027-12-31",{"name":130,"class":40},"Estrella Biopharma, Inc.",{"id":132,"slug":133,"hasResults":11,"nctId":134,"briefTitle":135,"officialTitle":136,"acronym":137,"eligibilityCriteria":138,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":139,"targetDuration":4,"studyType":141,"phases":4,"briefSummary":142,"conditions":143,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":144,"lastUpdatePostDateStruct":145,"startDateStruct":147,"completionDateStruct":149,"leadSponsor":151,"locationsCount":63},"100502928","climb-cns-lymphoma-imaging-and-molecular-biomarkers-study-100502928","NCT05828628","CLIMB: CNS Lymphoma Imaging and Molecular Biomarkers Study","A Prospective Imaging and Translational Tissue Study in CNS Lymphoma to Enable Further Disease Characterisation and the Development of Potential Predictive and Prognostic Biomarkers","CLIMB","Inclusion Criteria:\n\n* Subjects capable of giving informed consent, or if appropriate, if subject's capacity is deemed limited due to CNS involvement, a consultee can provide consent on their behalf. Some patients with PCNSL may be incapable of providing their own consent due to the neurological effects of their disease. In these cases the patient will be classed as an incapacitated adult and a legal representative will be sought in accordance with English or Scottish law as applicable (see 7.2.1)\n* A radiological or histological diagnosis of primary CNS lymphoma.\n* Have not received prior CNS directed therapy. Prior use of steroids is permitted.\n* Participants aged ≥18 years old.\n\nExclusion Criteria:\n\n\\- Involvement of lymphoma outside of the CNS",{"count":140,"type":21},36,"OBSERVATIONAL","A prospective imaging and translational tissue study in CNS lymphoma to enable further disease characterisation and the development of potential predictive and prognostic biomarkers.",[28],"2025-06-05",{"date":146,"type":33},"2025-06-11",{"date":148,"type":33},"2023-09-18",{"date":150,"type":21},"2031-09",{"name":152,"class":62},"Royal Marsden NHS Foundation Trust",{"id":154,"slug":155,"hasResults":11,"nctId":156,"briefTitle":157,"officialTitle":158,"acronym":4,"eligibilityCriteria":159,"healthyVolunteers":11,"sex":16,"minAge":160,"maxAge":161,"enrollmentInfo":162,"targetDuration":4,"studyType":22,"phases":164,"briefSummary":165,"conditions":166,"keywords":4,"overallStatus":167,"whyStopped":4,"lastUpdateSubmitDate":168,"lastUpdatePostDateStruct":169,"startDateStruct":171,"completionDateStruct":173,"leadSponsor":175,"locationsCount":4},"100585410","phase-2-methotrexate-or-thiotepa-combined-with-r-chop-and-orelabrutinib-in-cnsl-patients-100585410","NCT06901999","Methotrexate or Thiotepa Combined With R-CHOP and Orelabrutinib in CNSL Patients","Efficacy and Safety of Methotrexate (MTX) or Thiotepa (for MTX-Intolerant Patients) Combined With R-CHOP and Orelabrutinib in the Treatment of Systemic DLBCL With Central Nervous System Involvement","Inclusion Criteria:\n\n* Fully understand the study and voluntarily sign the informed consent form.\n* Age: 14-80 years.\n* Expected survival of more than 3 months, as determined by the investigator.\n* Pathologically or cytologically confirmed diffuse large B-cell lymphoma (DLBCL) of B-cell origin through pathology or flow cytometry.\n* Central nervous system (CNS) involvement, confirmed by at least one of the following:\n\n  1. Symptoms related to CNS involvement.\n  2. Abnormal findings on imaging.\n  3. Pathological evidence (positive cerebrospinal fluid cytology, positive brain lesion biopsy or positive cerebrospinal fluid ctDNA).\n* Any non-hematologic toxicity related to prior treatments must have resolved to Grade 1 or normal levels (per NCI CTCAE Version 5.0), except for alopecia.\n* Bone marrow and organ function must meet the following criteria (without blood transfusion, G-CSF administration, or pharmacological correction within 14 days prior to screening):\n\nBone marrow function:\n\n1)Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹\u002FL. 2)Platelet count ≥ 50 × 10⁹\u002FL. 3)Hemoglobin ≥ 60 g\u002FL.\n\n* Liver function:\n\n  1. Total bilirubin ≤ 1.5 × ULN (≤ 3.0 × ULN if liver metastasis is present).\n  2. AST and ALT ≤ 2.5 × ULN (≤ 5.0 × ULN if liver metastasis is present).\n* Coagulation function:\n\nInternational normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.\n\n• Renal function: Serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance rate ≥ 30 mL\u002Fmin (calculated using the Cockcroft-Gault formula): Male: Cr (mL\u002Fmin) = (140 - age) × weight (kg) \u002F \\[72 × serum creatinine (mg\u002FdL)\\]. Female: Cr (mL\u002Fmin) = (140 - age) × weight (kg) \u002F \\[85 × serum creatinine (mg\u002FdL)\\].\n\n* Women of childbearing potential (WOCBP) and men with reproductive potential must agree to use effective contraception during the study and for 3 months after discontinuing treatment.\n* Good compliance, with willingness to adhere to visit schedules, dosing regimens, laboratory tests, and other study procedures.-\n\nExclusion Criteria:\n\n* Contraindications to any of the drugs included in the treatment regimen.\n* History of active liver disease, including viral or other hepatitis or liver cirrhosis (Hepatitis B is defined as HBV-DNA exceeding the upper limit of normal; active Hepatitis C is defined as seropositive for HCV antibodies, but patients with HCV-RNA negative results can be included).\n* Human immunodeficiency virus (HIV) infection.\n* Congestive heart failure classified as greater than NYHA Class II by the New York Heart Association; history of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within the past six months.\n* Congenital long QT syndrome or QTc \\> 480 ms (Note: QTc must be calculated using Friederica's formula: QTcF = QT \u002F (RR)\\^0.33).\n* Pregnant or breastfeeding women, or those planning to become pregnant during the study.\n* History of confirmed neurological or psychiatric disorders, or a history of substance abuse or drug addiction.","14 Years","80 Years",{"count":163,"type":21},23,[25],"This study is designed as an open-label, prospective, single-arm, single-center trial aimed at evaluating the efficacy and safety of MTX or Thiotepa combined with Orelabrutinib and standard chemotherapy regimens in the treatment of DLBCL patients with central nervous system involvement.",[28],"NOT_YET_RECRUITING","2025-03-28",{"date":170,"type":33},"2025-03-30",{"date":172,"type":21},"2025-04",{"date":174,"type":21},"2028-11",{"name":176,"class":62},"Ruijin Hospital",{"id":178,"slug":179,"hasResults":11,"nctId":180,"briefTitle":181,"officialTitle":182,"acronym":4,"eligibilityCriteria":183,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":184,"targetDuration":4,"studyType":22,"phases":186,"briefSummary":187,"conditions":188,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":189,"lastUpdatePostDateStruct":190,"startDateStruct":192,"completionDateStruct":194,"leadSponsor":196,"locationsCount":197},"100583466","phase-2-relma-cel-followed-by-tislelizumab-for-the-treatment-of-relapsedrefractory-cns-large-b-cell-lymphoma-100583466","NCT06876688","Relma-cel Followed by Tislelizumab for the Treatment of Relapsed\u002FRefractory CNS Large B-Cell Lymphoma","Relmacabtagene Autoleucel Injection Followed by Tislelizumab for the Treatment of Relapsed\u002FRefractory Large B-Cell Lymphoma Involved in the Central Nervous System","Inclusion Criteria:\n\n1. Age greater than or equal to 18 years old, male or female;\n2. Relapsed or refractory CNS-involved large b-cell lymphoma after at least first-line therapy, with an efficacy assessment of CR or PR after salvage therapy, and current stable efficacy status;\n3. Eastern Cooperative Oncology Group (ECOG) score of 0-2;\n4. Have a life expectancy of ≥ 12 weeks\n5. Use contraception\n6. Have adequate bone marrow and organ function:\n\n   1. Neutrophil count (anc) ≥1.0 x 109\u002FL;\n   2. Hemoglobin ≥ 8.0 g\u002Fdl;\n   3. Platelet count ≥ 50 x 109\u002FL;\n   4. Total bilirubin ≤ 1.5 × upper limit of normal (ULN)\n   5. Alanine aminotransferase\u002Faspartate aminotransferase (ALT\u002FAST) ≤ 2.5 x ULN or ≤ 5 x ULN (in the presence of hepatic invasion);\n   6. Creatinine clearance ≥40mL\u002Fmin\n   7. Lipase ≤ 1.5 x ULN\n\nExclusion Criteria:\n\n1. Severe active central nervous system symptoms\n2. Prior chimeric antigen receptor cellular immunotherapy targeting cd19\n3. Known human immunodeficiency virus (hiv) infection or positive immunoassay;\n4. Live vaccination within 30 days prior to study drug administration;\n5. Active autoimmune disease requiring systemic therapy in the last 12 months\n6. Allergy to the study drug or history of severe allergic reactions\n7. Potential risk of malignant cardiac arrhythmia\n8. History of stroke or intracranial hemorrhage within 3 months prior to the date of administration of study medication\n9. Other malignant tumors presently or within 3 years prior to enrollment\n10. Conditions that, in the judgment of the investigator, would interfere with full participation in the study; pose a significant risk to the subject; or interfere with the interpretation of the study data\n11. Pregnant or lactating patients;",{"count":185,"type":21},30,[25],"This study aims to evaluate the efficacy and safety of Relma-cel in the treatment of central nervous system lymphoma (CNSL), as well as its pharmacokinetic characteristics. Enrolled patients with relapsed\u002Frefractory (R\u002FR) CNSL will receive Relma-cel infusion, followed by Tislelizumab treatment (200mg, IV, q4w, for 12 months) starting on day 35 after infusion. Bruton's tyrosine kinase (BTK) inhibitors will be used in combination as needed. The follow-up period will last for 4 years, monitoring drug safety, disease status, survival, and the pharmacokinetic characteristics of Relma-cel.",[28],"2025-03-10",{"date":191,"type":33},"2025-03-14",{"date":193,"type":33},"2023-11-30",{"date":195,"type":21},"2028-11-30",{"name":176,"class":62},6,{"id":199,"slug":200,"hasResults":11,"nctId":201,"briefTitle":202,"officialTitle":203,"acronym":4,"eligibilityCriteria":204,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":205,"targetDuration":4,"studyType":22,"phases":207,"briefSummary":208,"conditions":209,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":212,"lastUpdatePostDateStruct":213,"startDateStruct":215,"completionDateStruct":217,"leadSponsor":219,"locationsCount":63},"100466273","phase-1-tafasitamab-plus-lenalidomide-in-relapsed-cns-lymphoma-100466273","NCT05351593","Tafasitamab Plus Lenalidomide in Relapsed CNS Lymphoma","A Phase I\u002FII Study of Tafasitamab Plus Lenalidomide in Relapsed CNS Lymphoma","Inclusion Criteria:\n\n1. Participants must have relapsed primary or secondary CNS lymphoma, diffuse large B-cell lymphoma (DLBCL) type, based on radiographic, ophthalmologic, or CSF criteria (evidence of malignant cells based on CSF studies: cytospin\u002Fcytology and flow-cytometry).\n\n   1. Concomitant systemic lymphoma as well as transformation from follicular lymphoma and\u002For Chronic lymphocytic leukemia (CLL) to an aggressive B-cell histology is allowed.\n   2. Participants are eligible with disease in each CNS compartment: brain, leptomeninges\u002FCSF and intraocular compartment.\n2. Age \\>= 18 years.\n3. Anticipated survival \\> 2 months, as determined by the investigator.\n4. Eastern Cooperative Oncology Group (ECOG) performance status \\\u003C=1 (Karnofsky performance status \\>= 70%)\n5. Demonstrates adequate organ function as defined below:\n\n   1. Absolute neutrophil count (ANC) ≥ 1.5 X 10\\^9\u002F L (1,500\u002F microliter (mcL), growth factors permitted).\n   2. Platelets \\>= 50 X 10\\^9 \u002F L (50,000\u002F mcL, platelet transfusion independent).\n   3. Total bilirubin \\\u003C= 1.5 x institutional upper limit of normal,unless elevated due to Gilbert's syndrome.\n   4. Aspartate aminotransferase (AST)\u002Fserum glutamic-oxaloacetic transaminase (SGOT) \\\u003C=3 X institutional upper limit of normal.\n   5. Alanine aminotransferase (ALT)\u002Fserum glutamic-pyruvic transaminase (SGPT) \\\u003C=3 X institutional upper limit of normal.\n\n   d. Creatinine clearance (CrCl, calculated) \\>= 60 mL\u002Fmin\u002F1.73 m\\^2, calculated using the Cockcroft-Gault equation. CrCl \\> 60 mL\u002Fmin\u002F1.73 m2 is requisite for eligibility for the phase I dose-escalation phase of the study.\n6. Ability to understand and the willingness to sign a written informed consent document.\n7. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. If a HBV test comes up positive due to Intravenous immunoglobulin (IVIG) and the participant has no prior history of HBV, then perform a HBV PCR to confirm.\n\n   undetectable disease.\n8. Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. For individuals with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.\n9. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.\n10. The effects of the study drugs on the developing human fetus are unknown. For this reason, and because the teratogenic effect of lenalidomide in humans cannot be ruled out, females of child-bearing potential (FCBP) and men must agree to use adequate contraception. FCBP must agree to undergo pregnancy testing as required in the study protocol. Should a woman become pregnant or suspect they are pregnant while their partner is participating in this study, they should inform her treating physician immediately.\n11. Prior Therapies\n\n    1. Participants with CNS lymphoma involving the brain parenchyma must have received at least one prior systemic therapy.\n    2. Participants with secondary CNS lymphoma must have received prior CNS-directed treatment.\n    3. There is no limit in terms of prior lines of therapy received. Patients may have progressed after prior treatment with IMiD's (including lenalidomide, pomalidomide and CC122), patients may have had prior rituximab or other anti-CD20 based therapy as well as autologous and allogeneic stem cell transplant. Patients who progress after prior stem cell transplant are immediately eligible whereas patients that progress after anti-CD19-based therapy including CAR-T based therapy are not eligible.\n12. Recipients of prior hematopoietic stem cell transplant are eligible as long as the following criteria are met:\n\n    1. Absence of graft versus host disease.\n    2. Discontinuation of systemic immunosuppressant therapy.\n\nExclusion Criteria:\n\n1. Has received systemic anti-cancer therapies within 2 weeks of first dose, radiation within 1 week, antibody therapy within 4 weeks.\n2. Has not recovered from adverse events due to prior anti-cancer therapy to ≤ grade 1 or baseline (other than alopecia).\n3. Is currently receiving any other investigational agents.\n4. Has participated in a study of an investigational product and received study treatment or used an investigational device within four weeks of the first dose of treatment.\n5. Has a history of HIV infection.\n6. Has CNS post-transplant lymphoproliferative disease (PTLD).\n7. Has known hypersensitivity to lenalidomide or Tafasitamab.\n8. Pregnant women and women of child-bearing potential who will not using an effective method of birth control (detailed in Appendix 3) are excluded from this study because the study drugs have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenalidomide and\u002For Tafasitamab, breastfeeding should be discontinued if the mother is treated with study drugs.\n9. Prior receipt of anti-CD19 based therapy including anti-CD19, Chimeric antigen receptor T cells (CAR-T) therapy is an exclusion criteria.\n10. Has any significant medical condition or comorbidity that could compromise patient safety (e.g., uncontrolled serious infection).",{"count":206,"type":21},35,[24,25],"This is a single arm open-label multicenter phase I\u002FII investigation of combination lenalidomide\u002FTafasitamab in patients with relapsed central nervous system (CNS) lymphoma. This is the first study to examine a naked anti-CD19 monoclonal antibody in relapsed CNS lymphoma patients as well as the combination of anti-CD19 antibody plus an Immunomodulatory imide drugs (IMiDs) in CNS lymphomas. This study will also test the novel hypothesis that Tafasitamab enhances blood-brain barrier permeability, a potential property that could have broad clinical implications.",[28,210,211],"Primary Central Nervous System Lymphoma","Secondary Central Nervous System Lymphoma","2025-01-30",{"date":214,"type":33},"2025-02-03",{"date":216,"type":33},"2022-06-08",{"date":218,"type":21},"2026-06-30",{"name":220,"class":62},"James Rubenstein"]