[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"richter-transformation\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:richter-transformation":33},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,5,0,[8,73,113,152,168],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":35,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":61,"lastUpdatePostDateStruct":62,"startDateStruct":65,"completionDateStruct":67,"leadSponsor":69,"locationsCount":72},"100054189","phase-2-daly-ii-usa-mb-cart20191-for-dlbcl-100054189",false,"NCT04792489","DALY II USA\u002F MB-CART2019.1 for DLBCL","A Multi-center Single Arm Phase II Study to Evaluate the Safety and Efficacy of Genetically Engineered Autologous Cells Expressing Anti-CD20 and Anti-CD19 Specific Chimeric Antigen Receptor in Subjects With Relapsed and\u002For Refractory Diffuse Large B Cell Lymphoma","Inclusion Criteria:\n\n* Histologically confirmed B-cell non-Hodgkin's lymphoma:\n\n  * DLBCL cohort (both cohorts)\n* DLBCL or associated subtype, defined by WHO 2016 classification\n* DLBCL not otherwise specified (NOS)\n* High-grade B cell lymphoma with MYC and BCL2 and\u002For BCL6 rearrangements\n* High-grade B cell lymphoma (NOS)\n* Primary mediastinal (thymic) large B cell lymphoma\n* Transformed lymphoma (e.g., transformed follicular, or marginal zone lymphoma, follicular lymphoma (FL Grade 3)\n\n  o CNS cohort\n* B-cell primary or secondary central nervous system lymphoma (PCNSL or SCNSL)\n\n  o Mantle Cell Lymphoma (MCL) cohort\n* Histologically confirmed MCL determined by overexpression of cyclin D1 or presence of t(11;14) (q13; q32) translocation\n\n  o Richter's Transformation (RT) cohort\n* Histologically confirmed RT to a diffuse large B-cell lymphoma (DLBCL) subtype from underlying CLL (clonally related)\n* Relapsed or refractory disease is defined for DLBCL (and associated subtypes) population as:\n\nFor DLBCL cohort (after receiving at least two prior lines of therapy): persistent disease after failure of 2 or more lines of chemotherapy including rituximab or equivalent and anthracycline and either after failed ASCT, or ineligible, not intended for or not consenting to ASCT\n\n* Chemotherapy-refractory disease (applies to all cohorts) is defined as persistent disease after last line of therapy or relapsed or persistent disease after prior ASCT for lymphoma\n* Disease relapse in subjects without prior ASCT is defined as relapse of disease after the last dose of most recent therapy regimen\n\nFor disease specific cohorts added after the initial DLBCL cohort the definition of relapsed\u002Frefractory disease is as described below:\n\nCNS cohort: Subjects with relapsed\u002Frefractory PCNSL that have failed (or unable to tolerate) at least first-line therapy.\n\n* First-line therapy is defined as either high dose methotrexatebased therapy, temozolomide, high dose cytarabine, pemetrexed, lenalidomide or Bruton tyrosine kinase (BTK) inhibitor-based therapy.\n* No contraindications for MRI evaluation\n* CNS cohort: Subjects with SCNSL must have relapsed or refractory disease after having received at least one prior line of systemic therapy\n* Prior lines of systemic therapy should include an anti-CD20 monoclonal antibody and anthracycline containing chemotherapy regimen and\u002For with or without an autologous stem cell transplant\n\nMCL cohort: Subjects with relapsed\u002Frefractory disease after at least one prior systemic treatment, that must include:\n\n* Cytotoxic rituximab \\[or equivalent\\] based chemotherapy regimen (eg, rituximab bendamustine, R-CHOP, R-DHAP, R-ARA-C) AND\n* BTK inhibitor\n\nRT cohort: Subject must have relapsed\u002Frefractory disease after at least one prior systemic treatment following Richter's Transformation\n\nDLBCL transplant ineligible 2nd cohort: subject must have failure of first-line chemotherapy (including rituximab or equivalent and anthracycline).\n\n* For this cohort subjects are considered transplant ineligible if they meet one of the following criteria:\n* Age ≥70 years\n* ECOG status is 2 at screening\n* Impaired pulmonary function: diffusing capacity of the lung for carbon monoxide \\[DLCO\\] ≤ 60% adjusted for gender-specific hemoglobin concentration (Coates formula)\n* Impaired cardiac function: left ventricular ejection fraction (LVEF) \\\u003C 50%; must be assessed by echocardiogram or multiple uptake gated acquisition (MUGA) scan performed within 4 weeks of determination of eligibility\n* Impaired renal function: calculated creatinine clearance (Cockcroft and Gault) \\\u003C 60 mL\u002Fmin\n* Impaired hepatic function: aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) \\> 2 x upper limit of normal (ULN)\n\nIn addition, all subjects must have:\n\n* Age ≥18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening. ECOG performance status of 2 at screen is allowed if the decrease in performance status is due to lymphoma\n\n  * Subjects in DLBCL transplant-ineligible 2nd-line cohort with ECOG performance status of 2, regardless of attribution, will be allowed for inclusion\n* Measurable disease will be assessed by FDG-PET\u002FCT in systemic lymphoma . and by brain\u002Fspine MRI for CNS disease\n* Subject must have a tumor biopsy sample (at least 16 unstained slides of tissue or tissue block) from the most recent relapse available prior to MB-CART2019.1 infusion. If medically not feasible to obtain a biopsy from the most recent relapse and for cases when the amount of tissue is limited, the sponsor should be consulted, to confirm adequacy of the sample for study required analyses\n* No clinical suspicion of central nervous system (CNS) lymphoma (not applicable to CNS cohort)\n\n  * Subjects in DLBCL transplant-ineligible 2nd-line cohort with SCNSL will be allowed for inclusion\n* If the subject has history of CNS disease (not applicable to CNS cohort), then he\u002Fshe must have no signs or symptoms of CNS disease, have no active disease on magnetic resonance imaging (MRI), have no large cell lymphoma present in cerebral spinal fluid (CSF), regardless of the number of white blood cells (WBCs)\n* If has history of cerebral vascular accident (CVA), the CVA event must be greater than 12 months prior to leukapheresis. Any neurological deficits must be stable\n* A creatinine clearance (as estimated by direct urine collection or Cockcroft-Gault Equation) \\> 45mL\u002Fmin\n* Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA)\n* Subjects in DLBCL transplant-ineligible 2nd-line cohort with a lower ejection fraction of \\> 40% will be allowed for inclusion\n* Resting O2 saturation \\>90% on room air\n* Serum alanine aminotransferase (ALT) \u002F aspartate aminotransferase (AST)\\\u003C5 times the Upper Limit of Normal (ULN) for age\n* Total bilirubin \\\u003C1.5 mg\u002Fdl, except in individuals with Gilbert's syndrome\n* Subjects in DLBCL transplant-ineligible 2nd-line cohort with a total bilirubin of \\\u003C 2.0 mg\u002FdL will be allowed for inclusion\n* Absolute neutrophil count (ANC) \\> 1000\u002FμL\n* Absolute lymphocyte count \\> 100\u002FμL\n* Platelet count \\> 50,000\u002FµL\n* Estimated life expectancy of more than 3 months other than primary disease\n\nExclusion Criteria:\n\n* Primary CNS lymphoma (not applicable to CNS cohort)\n* Richter's transformed DLBCL arising from chronic lymphocytic leukemia (CLL) (not applicable to RT cohort)\n* Unable to give informed consent\n* Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B (HBsAg positive). If there is a history of treated hepatitis B or hepatitis C, the viral load must be quantitative polymerase chain reaction (PCR) negative; antiviral prophylaxis is required if HBsAg negative and anti-HBc positive\n* Known history of infection with hepatitis C virus (anti-HCV positive) unless viral load is undetectable per quantitative PCR and\u002For nucleic acid testing.\n* Pharmacologically uncontrolled seizures.\n* Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis, or other immunologic or inflammatory disease\n* Presence of CNS disorder that, in the judgment of the Investigator, may impair the ability to evaluate neurotoxicity. For CNS Cohort:\n\n  * For CNSL and DLBCL transplant-ineligible 2nd-line cohort patients that have a CNS lesion(s): Midline shift on MRI or Abnormal high CSF opening pressure and or CSF protein ≥150 mg\u002FdL Recent (within 3 months) whole brain radiotherapy (WBRT) are exclusionary\n* Active systemic fungal, viral, or bacterial infection\n* Pregnant or breast-feeding woman\n* Previous or concurrent malignancy with the following exceptions:\n\n  * Adequately treated basal cell or squamous cell carcinoma (adequate wound healing required prior to study entry)\n  * In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 2 years prior to the study\n  * Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron or tamoxifen and in clinical remission of ≥ 2 years\n  * A primary malignancy which has been completely resected \u002F treated with curative intent and in complete remission of ≥ 2 years\n* Severely immunocompromised subjects e.g., due to current treatment of non-neurologic autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus).\n* Medical condition requiring prolonged use of systemic corticosteroids equivalent to prednisone \\>10 mg\u002Fday. For CNS cohort: Up to 2 mg\u002Fday dexamethasone (or equivalence) may be allowed at any time, higher doses allowed up to 7 days prior to apheresis or after apheresis until lymphodepletion.\n* History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment.\n* Concurrent radiotherapy (allowed up to time of lymphodepletion). For prior systemic therapy, at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed at the time of scheduled leukapheresis.\n* Baseline dementia that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline.\n* History of severe immediate hypersensitivity reaction to any of the agents used in this study.\n* Refusal to participate in additional lentiviral gene therapy long-term follow-up (LTFU) protocol\n* Prior CAR-T therapy for any indication or systemic gene modifying therapy for B-cell lymphoma\n* Prior allogeneic stem cell transplant for any indication\n* Prior Bispecific T cell engaging (BITE) antibodies for cancer therapy\n* Prior T cell receptor-engineered T cell therapy","ALL","18 Years",{"count":19,"type":20},315,"ESTIMATED","INTERVENTIONAL",[23],"PHASE2","DALY II USA is a phase II, multi-center, single arm study to evaluate the efficacy, safety, and pharmacokinetics of zamtocabtagene autoleucel (MB-CART2019.1) in patients with relapsed and\u002For refractory B cell lymphoma (BCL). Cohorts include subjects with diffuse large B-cell lymphoma (DLBCL) after receiving at least 2 lines of therapy, primary or secondary central nervous system (CNS) lymphoma (PCNSL) and (SCNSL) after receiving at least one line of therapy, mantle cell lymphoma (MCL) and Richter's transformation (RT) after receiving at least one line of therapy, and DLBCL transplant-ineligible after receiving at least one line of therapy.",[26,27,28,29,30,31,32,33,34],"Refractory Diffuse Large B Cell Lymphoma (DLBCL)","Relapsed Diffuse Large B Cell Lymphoma","High Grade B-cell Lymphoma (HGBCL)","Primary Mediastinal B-cell Lymphoma (PMBCL)","Transformed Lymphoma","Central Nervous System Lymphoma","Mantle Cell Lymphoma (MCL)","Richter Transformation","Transplant-ineligible 2nd Line DLBCL",[36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59],"CD19\u002FCD20-directed CAR-T Cells","Zamtocabtagene autoleucel","B-Cell Non-Hodgkin Lymphoma","Primary Central Nervous System Lymphoma","Secondary Central Nervous System Lymphoma","NHL","PCNSL","SCNSL","Chimeric Antigen Receptor","CAR","CAR-T Cell","Autologous T Cell Therapy","Central Nervous System Neoplasms","Lymphoma","Lymphoma, Non-Hodgkin","Lymphoma, B-Cell","Lymphoma, Large B-Cell, Diffuse","MCL","RT","CLL","Immunotherapy","T cells","T cell infusion","transplant-ineligible 2nd line DLBCL","RECRUITING","2026-07-09",{"date":63,"type":64},"2026-07-13","ACTUAL",{"date":66,"type":64},"2021-05-25",{"date":68,"type":20},"2028-12-31",{"name":70,"class":71},"Miltenyi Biomedicine GmbH","INDUSTRY",32,{"id":74,"slug":75,"hasResults":11,"nctId":76,"briefTitle":77,"officialTitle":78,"acronym":4,"eligibilityCriteria":79,"healthyVolunteers":11,"sex":16,"minAge":80,"maxAge":4,"enrollmentInfo":81,"targetDuration":4,"studyType":21,"phases":83,"briefSummary":85,"conditions":86,"keywords":99,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":103,"lastUpdatePostDateStruct":104,"startDateStruct":106,"completionDateStruct":108,"leadSponsor":110,"locationsCount":112},"100421728","phase-1-study-of-oral-administration-of-lp-118-in-patients-with-relapsed-or-refractory-cll-sll-mds-mdsmpn-aml-cmml-2-mpn-bp-all-mf-nhl-rt-mm-or-t-pll-100421728","NCT04771572","Study of Oral Administration of LP-118 in Patients With Relapsed or Refractory CLL, SLL, MDS, MDS\u002FMPN, AML, CMML-2, MPN-BP, ALL, MF, NHL, RT, MM or T-PLL.","A Phase 1\u002F1b Study Evaluating the Safety, Pharmacokinetics, and Preliminary Efficacy of LP-118 in Subjects With Relapsed or Refractory Hematological Malignancies","Inclusion Criteria:\n\n1. Male or female subjects, ≥ 18 years of age at the time of Screening with the following exception as outlined below:\n\n   -For T cell and B cell ALL subjects with age between 13 - 18 years, their body weight shall be ≥ 40 kg.\n2. Eligible subject must have an advanced hematologic malignancy including:\n\n   Group 1:\n\n   Group 1a\n   * Relapsed or refractory low risk tumor lysis CLL\u002FSLL subjects (ALC \\\u003C 25 x 109 cells\u002FL and all lymph nodes \\\u003C 5 cm) who have received at least two prior therapies. Subjects may also have slowly progressed on irreversible BTK inhibitors while on treatment with these agents.\n   * For CLL\u002FSLL subjects who come off BCR antagonist treatment (BTK inhibitors, P13K inhibitors, etc.) allows washout for 2 days as these subjects, progress quickly after treatment discontinuation and then remain eligible (steroids may be given during these two days to allow disease control).\n\n   Group 1b\n   * Morphologically confirmed diagnosis of MF in accordance with the WHO 2016 revised criteria, that is relapsed, intolerant, and\u002For refractory and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits;\n   * Morphologically confirmed diagnosis of MDS\u002FMPN, excluding juvenile myelomonocytic leukemia (JMML), in accordance with WHO 2016 revised criteria, that is relapsed and\u002For refractory and that, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits;\n   * Chronic myelomonocytic leukemia (CMML) with \\\u003C9% blasts;\n   * Or atypical chronic myeloid leukemia (aCML) with Hgb \\> 10g\u002FdL, WBC count \\\u003C 50 x 109 cells\u002FL, \\\u003C10% immature circulating cells;\n   * Or MDS\u002FMPN with ring sideroblasts and thrombocytosis (MDS\u002FMPN-RS-T) with Hgb \\> 10g\u002FdL;\n   * Or myelodysplastic\u002Fmyeloproliferative neoplasm, unclassifiable (MDS\u002FMPN-UC)\n   * CMML-2 with 10-19% blasts as defined by WHO 2016 revised criteria that is relapsed and\u002For refractory to prior HMA therapy;\n   * Relapsed and\u002For refractory MPN-BP as defined by WHO 2016 revised criteria that is transformed MPN with \\>20% myeloid blasts in the peripheral blood or bone marrow, in the opinion of the Investigator, subjects who have no available therapies known to provide clinical benefits;\n   * MDS subjects with refractory anemia with excess blasts (MDS-EB; subtype MDS-EB-1 or MDS-EB-2) as defined by WHO 2016 revised criteria and\u002For MDS with high- or very high-risk (risk score \\> 4.5) per the Revised International Prognostic Scoring System (IPSS-R, refer to Appendix 11; Section 15.13) who have no available therapies known to provide clinical benefit;\n   * Relapsed or refractory AML subjects (including de novo AML, secondary AML evolving from MDS or MPN or other antecedent hematologic disorder, and therapy-related AML) as defined by WHO 2016 revised criteria, subjects who have no available therapies known to provide clinical benefits; subjects with prior BCL-2 inhibitor therapy are permitted. WBC needs to be ≤ 25 × 109 cells\u002FL at the time of initiating investigational therapy (hydroxyurea is allowed to control WBC prior to and during therapy).\n\n   Group 1c\n   * Relapsed or refractory low risk tumor lysis NHL (NHL histologies \\[MZL, FL, WM, DLBCL, ATLL, PTCL, AITL, ALCL, MCL\\] are to be included per the 2016 World Health Organization \\[WHO\\] criteria) subjects, must have histologically documented diagnosis of a non-Hodgkin lymphoma as defined in the WHO classification scheme. Subjects have received at least 2 prior therapies and have no available therapies known to provide clinical benefit; For subjects with indolent NHL (Grade 1\\~3a FL, MZL) who have received two prior systemic therapies and have relapsed or progressed according to 2014 Lugano;\n   * Low risk tumor lysis transformed follicular, MZL, WM (to large cell or aggressive lymphoma) subjects who must have received at least one prior systemic therapy for the transformed lymphoma (unless combination chemotherapy is not appropriate);\n   * Low risk tumor lysis Richter transformation (RT): previously treated CLL and biopsy-proven Richter transformation with DLBCL histology after receiving at least one regimen for RT;\n   * Relapsed or refractory multiple myeloma (MM) subjects who have received a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 and have no treatment options available known to provide clinical benefit;\n   * Low risk tumor lysis T-cell prolymphocytic leukemia (T-PLL) subjects who have received one therapy for this and are relapsed or refractory;\n\n   Group 1d\n   * Relapsed or refractory ALL with dexamethasone run-in \\[5 days, dexamethasone 10mg\u002Fm2 (divided BID)\\];\n   * Or r\u002Fr ALL in remission but with detectable MRD (MRD +) by any detection method per institution standard of practice;\n   * IT chemo (per institutional SOC) is permitted prior to LP-118 C1D1 dosing, and then concomitantly on treatment if in best interest of the subject;\n   * Relapsed or refractory ALL subjects with B cell phenotype who have received at least two prior therapeutic regimens (such as multi-agent chemotherapy and\u002For tyrosine kinase inhibitors including bosutinib, dasatinib, imatinib, nilotinib or ponatinib) and failed, or are currently ineligible\u002Fintolerant for CD19-based target therapy (e.g. Blinatumomab); Relapsed or refractory ALL subjects with T cell phenotype who have received at least one prior therapy and failed.\n   * Relapsed or refractory ALL subjects with age between 13 - 18 years and have body weight ≥ 40kg, ALL subjects with B cell phenotype who have received at least two prior therapeutic regimens (such as multi-agent chemotherapy and\u002For tyrosine kinase inhibitors including bosutinib, dasatinib, imatinib, nilotinib or ponatinib) and progressed, or are currently ineligible\u002Fintolerant for CD19-based target therapy (e.g. Blinatumomab); Relapsed or refractory ALL subjects with T cell phenotype who have received at least one prior therapy and progressed.\n\n   Group 2\n   * Relapsed or refractory intermediate and high risk tumor lysis CLL\u002FSLL subjects who have received at least two prior therapies;\n   * Relapsed or refractory intermediate and high risk tumor lysis NHL (NHL histologies \\[MZL, FL, WM, DLBCL, ATLL, PTCL, AITL, ALCL, MCL\\] are to be included per the 2016 World Health Organization \\[WHO\\] criteria) subjects, must have histologically documented diagnosis of a non-Hodgkin lymphoma as defined in the WHO classification scheme. Subjects have received at least 2 prior therapies and have no available therapies known to provide clinical benefit; For subjects with indolent NHL (Grade 1\\~3a FL, MZL) who have received two prior systemic therapies and have relapsed or progressed according to 2014 Lugano;\n   * Intermediate and high risk tumor lysis transformed follicular, MZL, WM (to large cell or aggressive lymphoma) subjects who must have received at least one prior systemic therapy for the transformed lymphoma (unless combination chemotherapy is not appropriate);\n   * Intermediate and high risk tumor lysis Richter transformation (RT): previously treated CLL and biopsy-proven Richter transformation with DLBCL histology after receiving at least one regimen for RT;\n   * Intermediate and high risk tumor lysis T-cell prolymphocytic leukemia (T-PLL) subjects who have received one therapy for this and are relapsed or refractory;\n3. For Group 1d ALL subjects only, white blood cell (WBC) count ≤ 25 × 109 cells\u002FL at the time of enrollment (glucocorticoids or hydroxyurea is permitted to control WBC count prior to and during therapy).\n4. Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2.\n5. Adequate cardiac function defined as shortening fraction of ≥ 40% by 2D echocardiogram without Doppler.\n6. Subject must have adequate bone marrow (independent of growth factor support), coagulation, renal, and hepatic function, per laboratory reference ranges at Screening as follows:\n\n   Bone marrow criteria:\n   * Group 1 (r\u002Fr low risk tumor lysis CLL\u002FSLL (ALC \\\u003C 25 x 109 cells\u002FL and all lymph nodes \\\u003C 5 cm), NHL, RT, MM, T-PLL):\n   * Absolute Neutrophil Count (ANC) ≥ 1 x 109\u002FL (An exception is for subjects with an ANC\\\u003C1 x 109\u002FL and bone marrow heavily infiltrated with underlying disease)\n   * Platelets ≥ 50 x 109\u002FL on day of screening (entry platelet count must be independent of transfusion with 14 days of screening);\n   * Hemostasis criteria: Activated partial thromboplastin time (APPT) and prothrombin time (PT) ≤ 1.5 × the upper limit of normal (ULN);\n   * Renal function criteria: Serum creatinine ≤ ULN (per local institution reference range) or Calculated creatinine clearance (Cr Cl) ≥ 60 mL\u002Fmin using 24-hour CrCl OR by Cockcroft-Gault formula using actual body weight.\n   * Hepatic function criteria: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN; bilirubin ≤ 1.5 × ULN (except subjects with Gilbert's Syndrome, who may have a bilirubin \\> 1.5 × ULN, per discussion between the Investigator and the Medical Monitor).\n7. Females of childbearing potential (i.e., non-postmenopausal for at least 2 years or surgically sterile) and non-sterile males must practice at least 1 of the following methods of birth control with their partner(s) throughout the study and for 90 days after discontinuing study drug:\n\n   * Total abstinence from sexual intercourse as the preferred lifestyle of the subject; periodic abstinence is not acceptable;\n   * Surgically sterile partner(s) by vasectomy, bilateral orchiectomy, bilateral tubal ligation, bilateral oophorectomy or hysterectomy;\n   * Intrauterine device;\n   * Hormonal contraceptives (oral, parenteral, vaginal ring or transdermal) associated with inhibition of ovulation initiated for at least 1 month prior to study drug administration.\n8. Females of childbearing potential must have a negative pregnancy result as follows:\n\n   * At Screening on a serum sample obtained within 7 days prior to the first study drug administration, and\n   * Prior to dosing on a urine or serum sample obtained on the first day of study drug administration if ithas been \\> 7 days since obtaining the serum pregnancy test results in Screening.\n   * If a urine pregnancy test at any timepoint during the study is positive or indeterminate, a serum pregnancy test will be performed for confirmation\n9. Male subjects must refrain from sperm donation, from initial study drug administration until 90 days after the last dose of study drug.\n10. Subject must be able to understand and voluntarily sign and date an informed consent form (ICF), approved by an IRB, prior to any protocol-related procedures.\n\nExclusion Criteria:\n\nA subject will not be eligible for study participation if he\u002Fshe meets any of the following criteria.\n\n1. Subjects who have undergone autologous\u002Fallogeneic hematopoietic stem cell transplantation (HSCT) therapy within 60 days of the first dose of LP-118, or subjects on immunosuppressive therapy post-HSCT at the time of Screening, or currently with clinically significant graft-versus-host disease (GVHD) as per treating physician (Subjects in relapse after allogeneic transplantation must be off treatment with systemic immunosuppressive agents for at least 4 weeks. The use of topical steroids and\u002For up to 20 mg\u002Fday prednisone or equivalent systemic steroids for ongoing GVHD is permitted.\n2. Subject has a history of other malignancies within past 12 months that are active and could result in competing risks. These cases shall be discussed with the Medical Monitor with the exception below.\n\n   * Subject with breast cancer or prostate cancer on endocrine therapy with stable disease;\n   * Continuation of maintenance therapy in patients with adequately treated malignancy\n   * Adequately treated in situ carcinoma of the cervix uteri;\n   * Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;\n   * Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.\n   * Cancer with expected survival of 2 years or more or that will not confound evaluation of LP-118 treatment\n3. Subject has received any of the following therapies within 14 days or 5 half-lives (whichever is shorter) prior to the first dose of LP-118, or has not recovered to ≤ Grade 2 clinically significant AEs of the previous therapy (excluding neuropathy):\n\n   * Any anti-neoplastic therapy including chemotherapy, hormonal therapy, radiotherapy, biologic or immunotherapy, targeted small molecule agents, etc. (corticosteroid therapy \\\u003C 20 mg\u002Fday prednisone equivalent according to institutional guidelines to treat disease associated symptoms are permitted);\n   * For MF subjects who come off JAK2 antagonists, allow washout for 2 days as these subject's progress quickly after treatment discontinuation and remain eligible (steroids may be given during these two days to allow disease control).\n   * Subjects in need of immediate cytoreduction should be excluded.\n   * Any investigational therapy.\n   * Live vaccines\n4. Subject has received the following medications, therapies, or natural products within 7 days prior to the first dose of LP-118:\n\n   * Cytochrome P450, family 3, subfamily A (CYP3A) strong inhibitors (itraconazole, etc.), or substrates (Appendix 19);\n   * Subject has received strong Cytochrome P450, family 3, subfamily A (CYP3A) inducers within 14 days prior to the first dose of LP-118 (Appendix 19);\n   * Grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit;\n   * There is a 28-day washout period required for subjects who have had prior CAR-T treatment if there is no evidence of cytokine release syndrome (CRS) or other adverse events related to the CAR-T treatment, per discussion with the Medical Monitor.\n5. Subject has a significant history of renal, neurologic, psychiatric, pulmonary, endocrinologic, metabolic, immunologic, cardiovascular, or hepatic disease that, in the opinion of the Investigator, would adversely affect his\u002Fher participation in this study. Any other medical or social condition deemed by the investigator to be likely to interfere with a subject's ability to participate in the study, place the subject at unacceptable risk or interfere with the interpretation of the results. For subjects who have required surgical intervention for any above diseases within the past 6 months, a discussion with the Investigator and the Medical Monitor is needed.\n6. Subject has baseline prolongation of the heart rate-corrected QT (QTcF) interval ≥ 480 ms (calculated per Fridericia's formula \\[QTcF = QT\u002FRR (1\u002F3)\\])), a cardiovascular disability status of New York Heart Association Class ≥ 2 or associated other significant screening ECG or ultrasonic cardiogram abnormalities, per Investigator's judgement. For any subject with underlying RBBB or LBBB, cardiology review is needed to correct QTcF calculation using Sponsor recommended formula.\n7. Subject has significant a history of congenital long QT syndrome or Torsades de Pointes (TdP), uncontrolled or symptomatic arrhythmias, congestive heart failure, myocardial infarction, stroke, or intracranial hemorrhage within 6 months prior to the first dose of LP-118.\n8. Subject exhibits evidence of other clinically significant uncontrolled condition(s) including, but not limited to:\n\n   * Uncontrolled active systemic infection (bacterial, fungal, viral);\n   * Known poorly controlled human immunodeficiency virus (HIV) or active hepatitis B or C infection (active hepatitis B defined as HbsAg positive, or HbcAb positive with detectable HBV DNA load; active hepatitis C defined as HCV antibody positive with HCV RNA positive);\n   * Unexplained fever \\> 38.5°C within 7 days prior to the first dose of study drug administration (at the discretion of the Investigator if the fever is considered attributed to the subject's malignancy or an explained infection may be enrolled).\n9. A female subject is pregnant or breast-feeding.\n10. Subject incapacity to swallow oral medications, with any malabsorption condition, known dysphagia, short-gut syndrome, gastroparesis, or other conditions that, in the opinion of the Investigator, may limit the ingestion or gastrointestinal absorption, distribution, metabolism and excretion of drugs administered orally.\n11. Subjects with known and active central nervous system (CNS) involvement at Screening.\n12. Subjects with known hypersensitivity to any of the components of LP-118 (see Investigators Brochure for a list of components).\n13. Subjects who are taking QT-prolonging drugs that are known to cause Torsades de Pointes (TdP) (See Appendix 17 for the list of medications that are associated with TdP). In the event a prohibited medication might cause TdP, the PI must first determine if the risk to benefit is in favor of the subject and then discuss with the Medical Monitor about that particular medication on a case-by-case basis.\n14. Major surgery within 14 days prior to the first dose of study drug.","13 Years",{"count":82,"type":20},100,[84],"PHASE1","This is a Phase 1, multi-center, open-label study with a dose-escalation phase (Phase 1a) and a cohort expansion phase (Phase 1b), to evaluate the safety, tolerability, and PK profile of LP-118 under a once daily oral dosing schedule in up to 100 subjects.",[87,33,88,89,90,91,92,93,94,95,96,97,98],"Non Hodgkin Lymphoma","Multiple Myeloma","T-cell-prolymphocytic Leukemia","Acute Myeloid Leukemia","Acute Lymphocytic Leukemia","Myeodysplastic Syndrome","Myelodysplastic\u002FMyeloproliferative Neoplasm","Myelofibrosis","Chronic Lymphocytic Leukemia","Small Lymphocytic Lymphoma","Chronic Myelomonocytic Leukemia-2","Myelodysplastic Neoplasm in Blast Phase",[100,101,102],"Hematological Malignancies","Relapsed","Refractory","2026-04-29",{"date":105,"type":64},"2026-05-05",{"date":107,"type":64},"2022-05-08",{"date":109,"type":20},"2027-12-31",{"name":111,"class":71},"Newave Pharmaceutical Inc",8,{"id":114,"slug":115,"hasResults":11,"nctId":116,"briefTitle":117,"officialTitle":118,"acronym":4,"eligibilityCriteria":119,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":120,"targetDuration":4,"studyType":21,"phases":122,"briefSummary":123,"conditions":124,"keywords":138,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":142,"lastUpdatePostDateStruct":143,"startDateStruct":145,"completionDateStruct":147,"leadSponsor":149,"locationsCount":151},"100447533","phase-1-a-study-of-nx-1607-in-adults-with-advanced-malignancies-100447533","NCT05107674","A Study of NX-1607 in Adults With Advanced Malignancies","A Phase 1a, Dose Escalation, Safety and Tolerability Study of NX-1607, a Casitas B-lineage Lymphoma Proto-oncogene (CBL-B) Inhibitor, in Adults With Advanced Malignancies, With Phase 1b Expansion in Select Tumor Types","Key Inclusion Criteria:\n\n* Age ≥ 18 years.\n* Measurable disease per disease-specific response criteria.\n* Patients must have disease that is metastatic or unresectable and have received standard treatment options, are not candidates for standard treatment options, or will otherwise be prevented from receiving any standard treatment options.\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n* Minimum of 3 weeks or 5 half-lives (whichever is shorter) since last dose of systemic cancer therapy (unless otherwise specified) or minimum of 2 weeks since last radiotherapy, or minimum of 6 weeks since last systemic therapy with nitrosoureas, antibody-drug conjugate, or radio immuno-conjugate therapy.\n* Adequate organ and bone marrow function, in the absence of growth factors (with limited exception for DLBCL), as defined by laboratory parameters.\n* Patients of child-bearing potential must use adequate contraceptive measures to avoid pregnancy for the duration of the study as defined in the protocol.\n* Patient must be willing and able to adhere to the prohibitions and restrictions specified in the protocol.\n* Each patient must sign an informed consent form (ICF).\n* Histological or cytological diagnosis of platinum-resistant EOC, including primary peritoneal and fallopian tube carcinoma; gastric\u002FGEJ cancer; HNSCC; recurrent and either metastatic or unresectable melanoma; NSCLC; mCRPC; MPM; TNBC; locally advanced or metastatic urothelial cancer; cervical cancer; MSS CRC; or DLBCL (including DLBCL-RT)\n* Accessible tumor (for all cohorts) or lymph node (DLBCL only) for biopsy (Phase 1b only).\n\nKey Exclusion Criteria:\n\n* Active untreated brain metastases.\n* Patient has any of the following:\n* Uncontrolled intercurrent illness including, but not limited to, poorly controlled hypertension or diabetes, or ongoing active infection requiring systemic therapy.\n* Patients with primary refractory EOC defined as patients who do not respond to their first platinum-containing regimen or who relapse less than 6 months after completion of that first platinum-containing regimen\n* Psychiatric illness that would limit compliance with study requirements.\n* Treatment with any of the following prior to the first dose of NX-1607: CPI (anti-PD-1, PD-L1, cytotoxic T-lymphocyte-associated protein 4, etc) within 3 weeks; autologous or allogeneic stem cell transplant within 100 days; prior systemic cancer therapy within 3 weeks or 5 half-lives (whichever is shorter) (unless otherwise specified) (including hormonal therapy except for hormonal prophylaxis for a prior malignancy); prior radiotherapy within 2 weeks; prior systemic therapy with nitrosoureas, antibody-drug conjugate, or radio-immuno-conjugate therapy within 6 weeks; use of strong or moderate CYP3A4 inducers or inhibitors within 14 days or 7 days, respectively, or 5 half-lives (whichever is longer)\n* History of CAR-T therapy within 30 days prior to the first dose of NX-1607.\n* Toxicities from previous anti-cancer therapies that have not resolved to baseline levels or to Grade 1 or less except for Grade 2 alopecia and Grade 2 peripheral neuropathy or patients receiving endocrine replacement therapy\n* Patients who experienced Grade 3 or higher irAEs with prior immunotherapy.\n* History of uveitis, or an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.\n* Unable to swallow capsules or has malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction likely to interfere with the delivery, absorption, or metabolism of NX-1607.\n* Known allergies, hypersensitivity, or intolerance to components of NX-1607.\n* Pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of NX-1607.\n* Patient is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of NX-1607 and, as applicable, within 6 months after the last dose of paclitaxel.\n* Patient has had major surgery (e.g., requiring general anesthesia) within 4 weeks before the planned first dose of NX-1607, or will not have fully recovered from surgery, or has surgery planned during the time the patient is expected to participate in the study or within 4 weeks after the last dose of NX-1607. Note: Patients with minor planned surgical procedures to be conducted under local anesthesia may participate.\n* Vaccinated with a live vaccine within 28 days (with the exception of the annual inactivated influenza vaccine) or COVID-19 vaccination within 14 days prior to the first dose of NX-1607.\n* Active known second malignancy with the exception of any of the following:\n\n  * Adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer.\n  * Adequately treated Stage I cancer from which the patient is currently in remission and has been in remission for ≥ 2 years.\n  * Low-risk prostate cancer with Gleason score \\\u003C 7 and PSA \\\u003C 10 ng\u002FmL.\n  * Any other cancer from which the patient has been disease-free for ≥ 2 years.\n* Infection with human immunodeficiency virus (HIV)-1 or HIV-2. Exception: Patients with well controlled HIV (e.g., CD4 \\> 350\u002Fmm3 and undetectable viral load) are eligible.\n* Current active hepatitis, including hepatitis A (hepatitis A virus immunoglobulin M \\[IgM\\] positive), hepatitis B (hepatitis B virus \\[HBV\\] surface antigen positive), or hepatitis C (hepatitis C virus \\[HCV\\] antibody positive, confirmed by HCV RNA). Patients with HCV with undetectable virus after treatment are eligible. Patients with prior exposure to HBV may be entered if quantitative PCR is negative.\n* Use of systemic corticosteroids (\\> 20 mg prednisone or equivalent) within 15 days (except for prophylaxis for radio diagnostic contrast reactions and\u002For prophylaxis for patients receiving paclitaxel), or other immunosuppressive drugs within 30 days, prior to the first dose of NX-1607.\n* Use of biotin (i.e., Vitamin B7) or supplements containing biotin higher than the daily adequate intake of 30 µg \\[NIH 2020\\] (Note: Patients who switch from a high dose to a dose of 30 µg\u002Fday or less at least 1 day prior to Screening assessments are eligible for study entry).\n* Receipt of an IP or has been treated with an investigational device within 3 weeks or 5 half-lives (whichever is shorter) prior to the first dose of NX-1607.\n* Any of the following within 6 months prior to the first dose of NX-1607 or ongoing:\n\n  * Myocardial infarction\n  * Unstable angina\n  * Unstable symptomatic ischemic heart disease\n  * New York Heart Association Class III or IV heart failure\n  * Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, or symptomatic cerebrovascular events)\n  * Any other significant cardiac condition (e.g., pericardial effusion, restrictive cardiomyopathy, severe untreated valvular stenosis, or severe congenital heart disease)\n  * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating Investigator in consultation with the Medical Monitor.",{"count":121,"type":20},345,[84],"This is a first-in-human Phase 1a\u002F1b multicenter, open-label oncology study designed to evaluate the safety and anti-cancer activity of NX-1607 in patients with advanced malignancies.",[125,126,127,128,129,130,131,132,133,134,135,136,33,137],"Ovarian Cancer, Epithelial","Gastric Cancer","GastroEsophageal Junction (GEJ) Cancer","Head and Neck Squamous Cell Carcinoma","Metastatic or Unresectable Melanoma","Non-small Cell Lung Cancer (NSCLC)","Metastatic Castration-resistant Prostate Cancer (mCRPC)","Malignant Pleural Mesothelioma (MPM)","Triple Negative Breast Cancer (TNBC)","Metastatic Urothelial Carcinoma","Cervical Cancer","Diffuse Large B Cell Lymphoma (DLBCL)","Microsatellite Stable Colorectal Carcinoma",[139,140,141],"Ubiquitin Ligase Inhibitor","Advanced Malignancies","T-cell Activation","2025-09-05",{"date":144,"type":64},"2025-09-09",{"date":146,"type":64},"2021-09-29",{"date":148,"type":20},"2028-02-28",{"name":150,"class":71},"Nurix Therapeutics, Inc.",17,{"id":153,"slug":4,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":154,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":155,"targetDuration":4,"studyType":21,"phases":157,"briefSummary":158,"conditions":159,"keywords":160,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":161,"lastUpdatePostDateStruct":162,"startDateStruct":164,"completionDateStruct":165,"leadSponsor":166,"locationsCount":167},"100423333","Inclusion Criteria:\n\n* Histologically confirmed B-cell non-Hodgkin's lymphoma:\n* DLBCL DLBCL or associated subtype, defined by WHO 2016 classification:\n* DLBCL not otherwise specified (NOS)\n* High-grade B cell lymphoma with MYC and BCL2 and\u002For BCL6 rearrangements\n* High-grade B cell lymphoma (NOS)\n* Primary mediastinal (thymic) large B cell lymphoma\n* Transformed lymphoma (e.g., transformed follicular, or marginal zone lymphoma, follicular lymphoma (FL Grade 3)\n* CNS Cohort only: B-cell primary or secondary central nervous system lymphoma (PCNSL or SCNSL)\n* Mantle Cell Lymphoma (MCL) Cohort: Histologically confirmed MCL determined by overexpression of cyclin D1 or presence of t(11;14) (q13; q32) translocation\n* Richter's Transformation (RT) Cohort: Histologically confirmed Richter's transformation (RT) to a diffuse large B-cell lymphoma (DLBCL) subtype from underlying CLL (clonally related)\n* Relapsed or refractory disease is defined for DLBCL (and associated subtypes) population as failure of 2 or more lines of chemotherapy including rituximab or equivalent and anthracycline and either having failed autologous stem cell transplant (ASCT), or ineligible, not intended for or not consenting to ASCT\n* Chemotherapy-refractory disease is defined as persistent disease after last line of therapy or relapsed or persistent disease after prior ASCT for lymphoma\n* Disease relapse in subjects without prior ASCT is defined as relapse of disease after the last dose of most recent therapy regimen\n* CNS Cohort: Subjects with relapsed\u002Frefractory PCNSL that have failed (or unable to tolerate) at least first-line therapy.\n* No contraindications for MRI evaluation\n* CNS Cohort: Subjects with SCNSL must have relapsed or refractory disease after having received at least one prior line of systemic therapy\n* Prior lines of systemic therapy should include an anti-CD20 monoclonal antibody and anthracycline containing chemotherapy regimen and\u002For with or without an autologous stem cell transplant\n* No contraindications for MRI evaluation\n* MCL Cohort: Subjects with relapsed\u002Frefractory disease after at least one prior systemic treatment, that must include:\n* Cytotoxic rituximab-based chemotherapy regimen (eg, rituximab bendamustine, R-CHOP, R-DHAP, R-ARA-C) AND\n* BTK inhibitor\n* RT Cohort: Subject must have relapsed\u002Frefractory disease after at least one prior systemic treatment following Richter's Transformation\n* Age ≥18 years\n* Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening. ECOG performance status of 2 at screen is allowed if the decrease in performance status is due to lymphoma\n* Measurable disease according to Lugano 2014 criteria for assessing FDG-PET\u002FCT in systemic lymphoma (Cheson et al, 2014). Measurable disease according to IPCG criteria will be assessed by brain\u002Fspine MRI for CNS disease\n* Subject must have a tumor biopsy sample (at least 16 unstained slides of tissue or tissue block) from the most recent relapse available prior to MB-CART2019.1 infusion. If medically not feasible to obtain a biopsy from the most recent relapse and for cases when the amount of tissue is limited, the sponsor should be consulted, to confirm adequacy of the sample for study required analyses\n* No clinical suspicion of central nervous system (CNS) lymphoma (not applicable to CNS cohort)\n* If the subject has history of CNS disease (not applicable to CNS cohort), then he\u002Fshe must have no signs or symptoms of CNS disease, have no active disease on magnetic resonance imaging (MRI), have no large cell lymphoma present in cerebral spinal fluid (CSF), regardless of the number of white blood cells (WBCs)\n* If has history of cerebral vascular accident (CVA), the CVA event must be greater than 12 months prior to leukapheresis. Any neurological deficits must be stable\n* A creatinine clearance (as estimated by direct urine collection or Cockcroft-Gault Equation) \\> 45mL\u002Fmin\n* Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA)\n* Resting O2 saturation \\>90% on room air\n* Serum alanine aminotransferase (ALT) \u002F aspartate aminotransferase (AST)\\\u003C5 times the Upper Limit of Normal (ULN) for age\n* Total bilirubin \\\u003C1.5 mg\u002Fdl, except in individuals with Gilbert's syndrome\n* Absolute neutrophil count (ANC) \\> 1000\u002FμL\n* Absolute lymphocyte count \\> 100\u002FμL\n* Platelet count \\> 50,000\u002FµL\n* Estimated life expectancy of more than 3 months other than primary disease\n\nExclusion Criteria:\n\n* Primary CNS lymphoma (not applicable to CNS cohort)\n* Richter's transformed DLBCL arising from chronic lymphocytic leukemia (CLL) (not applicable to RT cohort)\n* Unable to give informed consent\n* Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B (HBsAg positive). If there is a history of treated hepatitis B or hepatitis C, the viral load must be quantitative polymerase chain reaction (PCR) negative; antiviral prophylaxis is required if HBsAg negative and anti-HBc positive\n* Known history of infection with hepatitis C virus (anti-HCV positive) unless viral load is undetectable per quantitative PCR and\u002For nucleic acid testing.\n* Pharmacologically uncontrolled seizures.\n* Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis, or other immunologic or inflammatory disease\n* Presence of CNS disorder that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity. For CNS Cohort:\n* Midline shift on MRI\n* Abnormal high CSF opening pressure and or CSF protein \\>150 mg\u002FdL Recent (within 3 months) whole brain radiotherapy (WBRT)\n* Active systemic fungal, viral, or bacterial infection\n* Pregnant or breast-feeding woman\n* Previous or concurrent malignancy with the following exceptions:\n* Adequately treated basal cell or squamous cell carcinoma (adequate wound healing required prior to study entry)\n* In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 2 years prior to the study\n* Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron or tamoxifen and in clinical remission of ≥ 2 years\n* A primary malignancy which has been completely resected \u002F treated with curative intent and in complete remission of ≥ 2 years\n* Severely immunocompromised subjects e.g., due to current treatment of non-neurologic autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus).\n* Medical condition requiring prolonged use of systemic corticosteroids equivalent to prednisone \\>10 mg\u002Fday. For CNS cohort: Up to 2 mg\u002Fday dexamethasone (or equivalence) may be allowed at any time, higher doses allowed up to 7 days prior to apheresis or after apheresis until lymphodepletion.\n* History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment\n* Concurrent radiotherapy (normal tissue sparing palliative radiotherapy allowed up to time of lymphodepletion). For systemic therapy, at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed at the time of scheduled leukapheresis.\n* Baseline dementia that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline\n* History of severe immediate hypersensitivity reaction to any of the agents used in this study\n* Refusal to participate in additional lentiviral gene therapy LTFU protocol\n* Prior CAR-T therapy for any indication or systemic gene modifying therapy for B-cell lymphoma\n* Prior allogeneic stem cell transplant for any indication\n* Prior BITE antibodies for cancer therapy\n* Prior T cell receptor-engineered T cell therapy",{"count":156,"type":20},248,[23],"DALY II USA is a phase II, multi-center, single arm study to evaluate the efficacy, safety, and pharmacokinetics of zamtocabtagene autoleucel (MB-CART2019.1) in patients with relapsed and\u002For refractory diffuse large B cell lymphoma (DLBCL) after receiving at least two lines of therapy. Additional cohorts include subjects with B-cell primary or secondary central nervous system (CNS) lymphoma (PCNSL) and (SCNSL), mantle cell lymphoma (MCL) and Richter's transformation (RT) after receiving at least one line of therapy.",[26,27,28,29,30,31,32,33],[36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58],"2025-04-21",{"date":163,"type":64},"2025-04-24",{"date":66,"type":64},{"date":68,"type":20},{"name":70,"class":71},25,{"id":169,"slug":170,"hasResults":11,"nctId":171,"briefTitle":172,"officialTitle":173,"acronym":174,"eligibilityCriteria":175,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":176,"targetDuration":4,"studyType":21,"phases":178,"briefSummary":179,"conditions":180,"keywords":4,"overallStatus":60,"whyStopped":4,"lastUpdateSubmitDate":181,"lastUpdatePostDateStruct":182,"startDateStruct":184,"completionDateStruct":186,"leadSponsor":188,"locationsCount":191},"100383384","phase-2-efficacy-and-safety-of-zanubrutinib-plus-tislelizumab-treatment-with-or-without-sonrotoclax-for-patients-with-richter-transformation-100383384","NCT04271956","Efficacy and Safety of Zanubrutinib Plus Tislelizumab Treatment with or Without Sonrotoclax for Patients with Richter Transformation","A Prospective, Open-label, Multicenter Phase-II Trial to Evaluate the Efficacy and Safety of Zanubrutinib (BGB-3111), a BTK Inhibitor, Plus Tislelizumab (BGB-A317), a PD1 Inhibitor, for Treatment of Patients with Richter Transformation with or Without Sonrotoclax（BGB-11417), a Bcl-2 Inhibitor (CLL-RT1-trial of the GCLLSG).","CLL-RT1","Inclusion Criteria:\n\n1. Confirmed diagnosis of CLL according to iwCLL criteria (Hallek et al, 2018)\n2. Confirmed histopathological diagnosis of RT (diffuse large B-cell lymphoma or Hodgkin's lymphoma \\[Hodgkin's lymphoma only when not eligible for more in-tensive treatment\\])\n3. Previously untreated RT or patients with objective response or non-tolerance to first-line RT treatment\n4. Adequate bone marrow function as defined by:\n\n   * Absolute neutrophil count (ANC) ≥ 1000\u002Fmm3, except for patients with bone marrow involvement in which ANC must be ≥ 500\u002Fmm3\n   * Platelet ≥ 75,000\u002Fmm3, except for patients with bone marrow involvement in which the platelet count must be ≥ 30,000\u002Fmm3\n5. Creatinine clearance ≥30ml\u002Fmin calculated according to the modified formula of Cockcroft and Gault or directly measured with 24hr urine collection or an equivalent method.\n6. Adequate liver function as indicated by a total bilirubin≤ 2 x, AST\u002FALT ≤ 2.5 x the institutional ULN value, unless directly attributable to the patient's CLL\u002FRT or to Gilbert's Syndrome, in which case a max. total bilirubin ≤ 3 x and AST\u002FALT ≤ 5 x the institutional ULN value are required.\n7. Negative serological testing for hepatitis B (HBsAg negative and anti-HBc nega-tive; patients positive for anti-HBc may be included if PCR for HBV DNA is negative and HBV-DNA PCR is performed every two months until 2 months af-ter last dose of zanubrutinib), negative testing for hepatitis-C RNA and negative HIV test within 6 weeks prior to registration\n8. Age at least 18 years\n9. ECOG performance status 0-2, ECOG 3 is only permitted if related to CLL or RT (e.g. due to anaemia or severe constitutional symptoms)\n10. Life expectancy ≥ 3 months\n11. Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements\n\nExclusion Criteria:\n\n1. Patients who did not respond to previous line of RT therapy (i.e. primary progressive patients)\n2. Patients with more than one prior line of RT therapy\n3. Allogenic stem cell transplantation within the last 100 days or signs of active GVHD after prior allogeneic stem cell transplantation within any time\n4. Patients with confirmed PML\n5. Uncontrolled autoimmune condition\n6. Malignancies other than CLL currently requiring systemic therapies (unless the malignant disease is in a stable remission at the discretion of the treating phy-sician)\n7. Uncontrolled infection currently requiring systemic treatment\n8. Any comorbidity or organ system impairment rated with a CIRS (cumulative ill-ness rating scale) score of 4, excluding the eyes\u002Fears\u002Fnose\u002Fthroat\u002Flarynx organ system , or any other life-threatening illness, medical condition or organ system dysfunction that - in the investigator´s opinion could comprise the patients safety or interfere with the absorption or metabolism of the study drugs\n9. Requirement of therapy with strong CYP3A4 inhibitors\u002F inducers\n10. Requirement of therapy with phenprocoumon or other vitamin K antagonists.\n11. Known active infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows:\n\n    * Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core anti-body (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    * Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable.\n12. Major surgery within 4 weeks of the first dose of study drug.\n13. Any uncontrolled or clinically significant cardiovascular disease including the following:\n\n    * Myocardial infarction within 6 months before screening\n    * Unstable angina within 3 months before screening\n    * New York Heart Association class III or IV congestive heart failure\n    * History of clinically significant arrhythmias (eg, sustained ventricular tachy-cardia, ventricular fibrillation, torsades de pointes)\n14. History of severe bleeding disorder such as hemophilia A, hemophilia B, von Willebrand disease, or history of spontaneous bleeding requiring blood trans-fusion or other medical intervention\n15. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug\n16. Severe or debilitating pulmonary disease\n17. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction\n18. Use of investigational agents, e.g. monoclonal antibodies or other experimental drugs within clinical trials, which might interfere with the study drug within 28 days (or 5 times half-life \\[t1\u002F2\\] of the compound, whichever is longer) prior to registration\n19. Known hypersensitivity to tislelizumab, zanubrutinib, sonrotoclax or any of the excipients\n20. Pregnant women and nursing mothers (a negative pregnancy test is required for all women of childbearing potential within 7 days before start of treatment)\n21. Fertile men or women of childbearing potential unless:\n\n    * surgically sterile or ≥ 2 years after the onset of menopause, or\n    * willing to use two methods of reliable contraception including one highly ef-fective contraceptive method (Pearl Index \\\u003C1) and one additional effective (barrier) method during study treatment and for 6 months after the end of study treatment.\n22. Vaccination with a live vaccine \\\u003C28 days prior to randomization\n23. Legal incapacity\n24. Prisoners or subjects who are institutionalized by regulatory or court order\n25. Persons who are in dependence to the sponsor or an investigator",{"count":177,"type":20},83,[23],"The aim of the CLL-RT1 trial is to evaluate the efficacy and safety of zanubrutinib (BGB-3111), a BTK inhibitor plus tislelizumab (BGB-A317), a PD1 inhibitor for treatment of patients with Richter Transformation",[33],"2024-12-27",{"date":183,"type":64},"2024-12-30",{"date":185,"type":64},"2020-02-19",{"date":187,"type":20},"2026-08",{"name":189,"class":190},"German CLL Study Group","OTHER",11]