[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"richter-syndrome\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:richter-syndrome":27},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,10,0,[8,41,67,91,123,146,171,193,217,242],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":29,"lastUpdatePostDateStruct":30,"startDateStruct":33,"completionDateStruct":35,"leadSponsor":37,"locationsCount":40},"100530428","phase-2-evaluation-of-treatment-by-glofitamab-in-combination-with-rituximab-or-obinutuzumab-plus-chop-in-patients-with-richter-syndrome-100530428",false,"NCT06186648","Evaluation of Treatment by Glofitamab in Combination With Rituximab or Obinutuzumab Plus CHOP in Patients With RIchter Syndrome","A Phase 2 Study Evaluating the Bispecific CD3xCD20 Antibody GLOfitamab in Combination With Rituximab or Obinutuzumab Plus Cyclophosphamide, Doxorubicin, Vincristine and Prednisone (CHOP) in Patients With RIchter Syndrome as Frontline therapY. A FILO Study","GLORIFY","Inclusion Criteria:\n\n1. Confirmed diagnosis of chronic lymphocytic leukemia or small lymphocytic lymphoma according to the revised iwCLL criteria with biopsy proven transformation to CD20 positive diffuse large B-cell lymphoma, consistent with RS according to the 2016 WHO classification\n2. A fresh or archival tissue biopsy is mandatory\n3. Previous therapy for CLL is allowed (but no prior therapy for RS)\n4. Age greater than or equal to 18 years and less or equal to 80 years\n5. ECOG performance status 0-2\n6. Participants must have at least one measurable target lesion (≥ 1.5 cm) in its largest dimension by computed tomography (CT) scan. Measurable disease, defined as at least one bi-dimensionally measurable nodal or tumor lesion, defined as \\> 1.5 cm in its longest dimension or PET-CT with at least one hypermetabolic lesion. Patients without measurable disease but with proven bone marrow infiltration by the RS are eligible.\n7. Patients must meet the following hematologic criteria at screening, unless they have significant bone marrow involvement of either CLL or RS cells confirmed on biopsy: absolute neutrophil count ≥ 1.5 G\u002FL, hemoglobin \\>10 g\u002FdL, and platelet count ≥75 G\u002FL independent of transfusion within 7 days of screening\n8. Subject must have adequate coagulation tests: Prothrombin Time \\> 50%, Fibrinogen \\> 1 g\u002FL\n9. Adequate liver function: Total bilirubin ≤ 1.5 x ULN; Aspartate aminotransferase (AST)\u002Falanine aminotransferase (ALT) ≤ 3 x ULN\n10. Adequate left ventricular ejection function (\\> 50 %)\n11. Adequate renal function: creatinine clearance calculated by MDRD\u002FCockcroft-Gault formula of ≥ 40 mL\u002Fmin\n12. Negative serologic or PCR test results for acute or chronic HBV infection\n13. Negative test results for HCV and HIV (Patients who are positive for HCV antibody must be negative for HCV by PCR to be eligible for study participation)\n14. Prior vaccination to the SARS-Cov-2 virus and and SARS-CoV-2 PCR testing and negative result before study treatment administration at each treatment cycle\n15. Negative serum or urinary pregnancy test within 7 days prior to study treatment in women of childbearing potential. Patients must agree to either remain completely abstinent or to use two effective contraceptive methods\\* until:\n\n    * If the patient is a male: at least 3 months after pre-treatment with obinutuzumab or RCHOP or 2 months after the last dose of glofitamab, whichever is longer. Men must refrain from donating sperm during this same period\n    * If patient is a female of childbearing potential: until at least 18 months after pre-treatment with obinutuzumab or RCHOP or 2 months after the last dose of glofitamab, whichever is longer\n16. Ability to understand and the willingness to sign a written informed consent document. Patient must be willing and able to comply with protocol-mandated hospitalization upon administration of the first dose of glofitamab. Patient must also be willing to comply with all study-related procedures\n17. Signed written informed consent\n18. Patient covered by any social security system\n\nExclusion Criteria:\n\n1. Patients with the Hodgkin variant of RS\n2. Patients with previously treated for RS\n3. Current or past history or presence of clinically relevant disorder affecting the central nervous system (CNS)\n4. Ineligible to CHOP full dose for any reason\n5. Previous treatment with a bispecific antibody\n6. Current or past history of DLBCL in the CNS (confirmed by CSF analysis)\n7. Steroids treatment (\\> 1 mg\u002Fkg\u002Fd for one week) before inclusion\n8. History of anaphylactic reactions to human, chimeric, or mouse monoclonal antibodies or to any components of the product.\n9. Prior allogeneic HSCT\n10. Patients with known acute infection or reactivation of a latent infection, whether bacterial, viral (including, but not limited to, EBV, cytomegalovirus (CMV), hepatitis B, hepatitis C, HIV and SARS-CoV-2), fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 4 weeks prior to the first study treatment.\n11. History of other malignancies, except: i) malignancy treated with curative intent and with no recurrence over the last 3 years ii) adequately treated non-melanoma skin cancer without evidence of disease iii) adequately treated carcinoma in situ without evidence of disease\n12. Prior solid organ transplantation\n13. History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows:\n\n    * Grade ≥ 3 adverse events with the exception of Grade 3 endocrinopathy managed with replacement therapy\n    * Grade 1-2 adverse events that did not resolve to baseline after treatment discontinuation\n14. Current uncontrolled autoimmune disease\\*\n15. History of human immunodeficiency virus\n16. Hepatitis B or C seropositivity (unless clearly due to vaccination)\n17. Pregnant or breastfeeding women\n18. Unwilling or unable to participate in all required study evaluations and procedures.\n19. Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form and authorization to use protected health information (in accordance with national and local subject privacy regulations)\n20. Persons deprived of their liberty by judicial or administrative decision, persons subject to a legal protection measure (guardianship, curatorship, legal protection), persons under psychiatric care\n21. Fertile male patients who cannot or do not wish to use an effective method of contraception, during and for 12 months after the final treatment used for the purposes of the study.\n22. Patients with history of macrophage activation syndrome (MAS) \u002F hemophagocytic lymphohistiocytosis (HLH)\n23. LVEF \\\u003C 50% as determined by echocardiography or multiple uptake gated acquisition (MUGA) scan, significant or extensive cardiovascular disease such as New York HeartAssociation Class III or IV cardiac disease or Objective Assessment Class C or D,myocardial infarction within the last 3 months, unstable arrhythmias, or unstable angina.\n24. Abnormal screening laboratory values as defined as following: a) ALT (SGOT) and\u002For ALT (SGPT) and\u002For ALP ≥ 3 x upper limit of normal (ULN); b) Total bilirubin ≥ 1.5 x ULN, unless due to Gilbert's disease; c) Creatinine ≥ 2.0 x ULN or creatinine clearance \\\u003C 40 mL\u002Fmin (calculated).\n25. Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)\n26. History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (or recombinant antibody-related fusion proteins)\n27. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug\n28. Major surgery or significant traumatic injury \\\u003C 28 days prior to the obinutuzumab infusion (excluding biopsies) or anticipation of the need for major surgery during study treatment\n29. Administration of a live, attenuated vaccine within 4 weeks before obinutuzumab infusion\n30. Treatment with another investigational agent or participating in another trial within 30 days prior to entering the study\n31. Clinically significant history of liver disease or cirrhosis\n32. Pregnant or breast-feeding or intending to become pregnant during the study\n33. No affiliation to social security\n34. Inability to comply with protocol mandated hospitalization and restrictions.","ALL","18 Years",{"count":20,"type":21},40,"ESTIMATED","INTERVENTIONAL",[24],"PHASE2","This is a national clinical trial, multicentric (28 centers), non-randomized phase 2 study.\n\nPopulation: Patients with previously untreated Richter's syndrome (RS), defined as the occurrence of an aggressive lymphoma (of diffuse large B-cell lymphoma histology) in a patient with chronic lymphocytic leukemia (CLL).\n\nStudy treatment:\n\nThe duration of each cycle is 21 days.\n\nCycle 1:\n\nParticipants will receive standard of care doses of R-CHOP in cycle 1 as follows:\n\n* Rituximab 375 mg\u002Fm² IV Day 1\n* Cyclophosphamide 750 mg\u002Fm² IV Day 1\n* Doxorubicin 50 mg\u002Fm² IV Day 1\n* Vincristine 1.4 mg\u002Fm² \\[capped at 2.0 mg\\] IV Day 1\n* Prednisone 60 mg\u002Fm2 per day PO Day 1-5\n\nCycle 2:\n\nIn order to minimize cytokine release syndrome (CRS), participants will then receive G-CHOP as cycle 2 (with obinutuzumab) and glofitamab:\n\n* Obinutuzumab 1000 mg single dose IV Day 1\n* Cyclophosphamide 750 mg\u002Fm² IV Day 1\n* Doxorubicin 50 mg\u002Fm² IV Day 1\n* Vincristine 1.4 mg\u002Fm² \\[capped at 2.0 mg\\] IV Day 1\n* Prednisone 60 mg\u002Fm2 per day PO Day 1-5\n* Glofitamab : administered intravenously (IV) as a step-up dose on Days 8 (2.5 mg) and 15 (10 mg)\n\nCycle 3-6:\n\nParticipants will receive standard of care doses of R-CHOP and Glofitamab as follows:\n\n* Rituximab 375 mg\u002Fm² IV Day 1\n* Cyclophosphamide 750 mg\u002Fm² IV Day 1\n* Doxorubicin 50 mg\u002Fm² IV Day 1\n* Vincristine 1.4 mg\u002Fm² \\[capped at 2.0 mg\\] IV Day 1\n* Prednisone 60 mg\u002Fm2 per day PO Day 1-5\n* Glofitamab : 30 mg IV Day 8\n\nCycle 7 and 8 (only for patient in Complete Response or Partial response after Cycle 6):\n\nCycle 7 and 8 consist of 2 infusions of glofitamab only at D8C7 and D8C8:\n\n● Glofitamab : 30 mg IV Day 8\n\nPrimary endpoint Percentage of participants with a complete response as assessed by the investigator using the Cheson IWG 2014 Lugano Classification (i.e. Deauville scale 1-3) after 6 cycles of R\u002FG-CHOP + glofitamab or at permanent treatment discontinuation.\n\nEnd of treatment is defined as after 6 cycles of R\u002FG-CHOP + glofitamab. Permanent treatment discontinuation is defined as the discontinuation of all treatments (R\u002FG-CHOP, glofitamab).",[27],"Richter Syndrome","RECRUITING","2026-06-29",{"date":31,"type":32},"2026-06-30","ACTUAL",{"date":34,"type":32},"2024-03-21",{"date":36,"type":21},"2029-09-04",{"name":38,"class":39},"French Innovative Leukemia Organisation","OTHER",23,{"id":42,"slug":43,"hasResults":11,"nctId":44,"briefTitle":45,"officialTitle":46,"acronym":4,"eligibilityCriteria":47,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":48,"targetDuration":4,"studyType":22,"phases":50,"briefSummary":52,"conditions":53,"keywords":4,"overallStatus":56,"whyStopped":4,"lastUpdateSubmitDate":57,"lastUpdatePostDateStruct":58,"startDateStruct":60,"completionDateStruct":62,"leadSponsor":64,"locationsCount":4},"100609869","phase-3-adding-pirtobrutinib-to-the-usual-treatment-for-people-with-newly-diagnosed-richter-transformation-the-piramid-trial-100609869","NCT07220187","Adding Pirtobrutinib to the Usual Treatment for People With Newly Diagnosed Richter Transformation, The PIRAMID Trial","A Randomized Phase III Study of Pirtobrutinib Plus R-CHOP vs. R-CHOP for Participants With Previously Untreated Richter Transformation (PIRAMID)","Inclusion Criteria:\n\n* Participants must have been diagnosed with Richter Transformation (RT) (CLL\u002Fsmall lymphocytic lymphoma \\[SLL\\] to LBCL)\n\n  * Participants must have histologically or cytologically confirmed LBCL\n* Participants must have measurable disease determined by PET\u002FCT or hematopathology (by morphology or flow cytometry) assessment within 42 days prior to registration\n* Participants must have staging PET\u002FCT imaging performed within 42 days prior to registration\n* Participants are allowed prior treatments for CLL\u002FSLL or its complications (autoimmune hemolytic anemia \\[AIHA\\], immune thrombocytopenic purpura \\[ITP\\]), with the exception of pirtobrutinib\n* Participants must not have prior treatment for Richter transformation except for corticosteroids up to equivalent dose of prednisone 700 mg total for less than 7 days for disease control. Treatment for CLL\u002FSLL with CLL\u002FSLL directed drugs (including BTK inhibitors with the exception of pirtobrutinib) after the Richter transformation diagnosis is allowed for the purpose of disease control. CLL targeted therapies must be stopped within 3 days before initiation of therapy on protocol. Chemotherapy or anti-CD20 monoclonal antibody therapy must be stopped within 2 weeks before initiation of therapy on protocol\n* Participants must not have contraindication for receiving anthracycline. Participants must not have received more than a cumulative dose of 100mg\u002Fm\\^2 in those participants who will receive R-CHOP or not more than 250 mg\u002Fm\\^2 in those participants who will receive R-mini-CHOP of prior doxorubicin (or equivalent dose of another anthracycline, such as epirubicin) therapy (at any time prior to registration)\n* Patients requiring strong CYP3A inducers are not eligible and can only be enrolled if\n\n  * an alternative treatment to the strong CYP3A inducer is available for them and\n  * the last dose of the strong CYP3A inducer is administered at least 7 days before initiation of pirtobrutinib for patients in safety run-in and arm 1\n* Participant must be ≥ 18 years old at the time of registration\n* Participant must have Eastern Cooperative Oncology Group (ECOG)\u002FZubrod Performance Status of 0-2\n* Participant must have a complete medical history and physical exam within 28 days prior to registration\n* Absolute neutrophil count (ANC) ≥ 0.75 x 10\\^3\u002FµL or ≥ 0.50 x 10\\^3\u002FµL in participants with suspected marrow involvement considered to impair hematopoiesis (within 28 days prior to registration)\n* Platelets ≥ 50 x 10\\^3\u002FµL or ≥ 30 x 10\\^3\u002FµL in participants with suspected marrow involvement considered to impair hematopoiesis (within 28 days prior to registration)\n* Hemoglobin ≥ 8 g\u002FdL (≥ 80 g\u002FL) or ≥ 6 g\u002FdL in participants with suspected bone marrow involvement considered to impair hematopoiesis (within 28 days prior to registration)\n* Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) or ≤ 3 x ULN with documented liver involvement and\u002For Gilbert's disease (within 28 days prior to registration)\n* Aspartate aminotransferase (AST) \u002F alanine aminotransferase (ALT) ≤ 3 × institutional ULN or ≤ 5 ULN with documented liver involvement (within 28 days prior to registration)\n* Participants must have a calculated creatinine clearance ≥ 30 mL\u002Fmin using the Cockcroft-Gault Formula. This specimen must have been drawn and processed within 28 days prior to registration. For the Cockcroft-Gault formula for calculated creatinine clearance, see the tools on the CRA Workbench https:\u002F\u002Ftxwb.crab.org\u002FTXWB\u002FTools.aspx\n* Participants must have a left ventricular ejection fraction (LVEF) ≥ 45% as measured by echocardiogram or radionuclide (MUGA) ventriculography within 56 days prior to registration\n* Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better\n* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Participants' HIV-directed therapy cannot have known interactions with pirtobrutinib\n* Participants with a known history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration\n* Participants with a known history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration\n* Participants must be able to swallow and retain oral medications and have no known gastrointestinal disorders likely to interfere with absorption of oral medications\n* Participants must not have a prior or concurrent malignancy in addition to CLL\u002FSLL and Richter transformation whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen\n* Participants must not have had major surgery within 28 days prior to registration\n* Participants must not have experienced a major bleeding event or grade ≥ 3 arrhythmia on prior treatment with a BTK inhibitor.\n\n  * NOTE: Major bleeding is defined as bleeding having one or more of the following features: potentially life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of at least 2g per deciliter; or bleeding in a critical area or organ (e.g., retroperitoneal, intraarticular, pericardial, epidural, or intracranial bleeding or intramuscular bleeding with compartment syndrome\n* Participants must not be pregnant or nursing (nursing includes breast milk fed to an infant by any means, including from the breast, milk expressed by hand, or pumped). Individuals who are of reproductive potential must have agreed to use an effective contraceptive method with details provided as a part of the consent process. A person who has had menses at any time in the preceding 12 consecutive months or who has semen likely to contain sperm is considered to be of \"reproductive potential.\" In addition to routine contraceptive methods, \"effective contraception\" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, bilateral tubal ligation\u002Focclusion, and vasectomy with testing showing no sperm in the semen\n* Participants must be offered the opportunity to participate in specimen banking\n* Participants must agree to have blood and lymphatic tissue specimens submitted for the integrated translational medicine study\n* For randomized participants only: Participants who can complete PRO-CTCAE and FACIT GP5 questionnaires forms in English or Spanish must be offered the opportunity to participate in the patient-reported outcome",{"count":49,"type":21},102,[51],"PHASE3","This phase III trial compares the effect of adding pirtobrutinib to the usual treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) to R-CHOP alone for the treatment of Richter transformation, which is when chronic lymphocytic leukemia or small lymphocytic lymphoma turns into large B-cell lymphoma, a more aggressive (faster-growing) form of lymphoma. Pirtobrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Adding pirtobrutinib to R-CHOP may kill more cancer cells than R-CHOP alone in patients with Richter transformation.",[27,54,55],"Transformed Chronic Lymphocytic Leukemia to Diffuse Large B-Cell Lymphoma","Transformed Small Lymphocytic Lymphoma to Diffuse Large B-Cell Lymphoma","NOT_YET_RECRUITING","2026-06-09",{"date":59,"type":32},"2026-06-11",{"date":61,"type":21},"2026-08-31",{"date":63,"type":21},"2036-10",{"name":65,"class":66},"SWOG Cancer Research Network","NETWORK",{"id":68,"slug":69,"hasResults":11,"nctId":70,"briefTitle":71,"officialTitle":72,"acronym":4,"eligibilityCriteria":73,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":74,"targetDuration":4,"studyType":22,"phases":76,"briefSummary":77,"conditions":78,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":81,"lastUpdatePostDateStruct":82,"startDateStruct":84,"completionDateStruct":86,"leadSponsor":88,"locationsCount":90},"100582445","phase-2-nemtabrutinib-and-pembrolizumab-for-the-treatment-of-richter-transformation-diffuse-large-b-cell-lymphoma-subtype-100582445","NCT06863402","Nemtabrutinib and Pembrolizumab for the Treatment of Richter Transformation, Diffuse Large B-cell Lymphoma Subtype","Nemtabrutinib and Pembrolizumab in Patients With Richter Transformation: A Phase II Study","Inclusion Criteria:\n\n* Patients with biopsy-proven Richter transformation, diffuse large B-cell lymphoma subtype (RT-DLBCL) from an antecedent or concurrently diagnosed chronic lymphocytic leukemia (CLL) and\u002For small lymphocytic lymphoma (SLL).\n* Be ineligible for frontline anthracycline-based chemoimmunotherapy (determined by treating investigator) OR have clinical evidence of disease progression after any prior treatment for RT-DLBCL.\n* Participants who have adverse events (AEs) due to previous anti-cancer therapies must have recovered to ≤ grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤ grade 2 neuropathy are eligible.\n\n  * Note: Participants who have lingering cytopenias from prior anti-cancer therapy or progressive disease may be eligible at the discretion of the study principal investigator (PI), provided they meet all other study criteria.\n* Have measurable disease as determined by imaging (by positron-emission tomography \\[PET\\] and\u002For computed tomography \\[CT\\] scans), immunohistochemistry, and\u002For flow cytometry, as per the Cheson criteria.\n* Have the ability to swallow and retain oral medication.\n* Age 18 years and older on the day of signing informed consent.\n* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.\n* Be free from other malignancy within 2 years prior to enrollment (with the exception of CLL\u002FSLL, low-risk and early stage \\[T1-T2a- Gleason score ≤ 6, and prostate-specific antigen \\[PSA\\] \\\u003C 10 ng\u002FmL\\] prostate cancer, or localized skin cancer that has undergone potentially curative therapy).\n* Absolute neutrophil count: ANC ≥ 500 cells\u002FµL (without G-CSF dose within the last 7 days prior to initiation of study treatment\n* Platelets: ≥ 25,000\u002FµL -not requiring transfusion within the last 3 days prior to initiation of study treatment). Patients on medications that increase bleeding risk (e.g. systemic anticoagulation, anti-platelet therapies, etc.) must have a platelet count ≥50,000 \u002FµL and have no history of major bleeding.\n* Hemoglobin: ≥ 7gm\u002FdL (transfusion support allowed).\n* Total bilirubin: ≤ 1.5 x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin levels \\> 1.5 x ULN.\n* Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase \\[SGOT\\])\u002Falanine aminotransferase (ALT)(serum glutamic-pyruvic transaminase \\[SGPT\\]): ≤ 2.5 x ULN (≤ 5 x ULN for participants with liver metastases).\n* Creatinine clearance (CrCl): ≥ 30 mL\u002Fmin (per Cockroft-Gault equation).\n* International normalized ratio (INR) (prothrombin \\[PT\\]\u002Factivated partial thromboplastin time \\[aPTT\\]): ≤ 1.5 x ULN, unless participant is receiving anticoagulant therapy, as long as PT or aPTT is within therapeutic range of intended use of anticoagulants.\n* Patients with history of human immunodeficiency virus (HIV) infection are potentially eligible (after conferring with the PI) if they meet ALL of the following criteria:\n\n  * Must have a CD4+ T-cell count ≥ 350 cells\u002Fmm\\^3 AND an HIV viral load below the detectable level as per locally available testing at the time of screening\n  * It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months.\n  * Participants on anti-retroviral therapy (ART) must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (day 1) and agree to continue ART throughout the study.\n  * The combination ART regimen must not contain any antiretroviral medications that interact with strong CYP3A4 inhibitors\u002Finducers\u002Fsubstrates (\\\u003Chttps:\u002F\u002Fwww.fda.gov\u002Fdrugs\u002Fdrug-interactions-labeling\u002Fdrug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers\\>). Participants receiving ART that are strong CYP3A4 inducers are not eligible to be included in the study.\n* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.\n\nNote: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis B screening tests, including HBsAg and hepatitis B core antibodies (anti-HBc), are required for all participants.\n\n* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening (Participants must have completed curative anti-viral therapy at least 4 weeks prior to the first administration of the study treatment).\n* A person of childbearing potential must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.\n* Participants of child-bearing potential must agree to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 6 months after the last dose of study medication. Should a person of child-bearing potential become pregnant or suspect they are pregnant while they or their partner is participating in this study, they should inform their treating physician immediately.\n* Participant must understand the investigational nature of this study and sign an Independent Ethics Committee\u002FInstitutional Review Board approved written informed consent form prior to receiving any study related procedure.\n\nExclusion Criteria:\n\n* Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX40, CD137).\n* Has received prior systemic anti-cancer therapy within 5 half-lives of last dose (or within 30 days for cellular therapy or investigational agents, or within 100 days post allogeneic hematopoietic stem cell transplantation and without any grade ≥ 2 graft versus host disease) prior to enrollment.\n* Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-central nervous system (CNS) disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.\n* Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed or messenger ribonucleic acid (mRNA) vaccines is allowed.\n* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (daily dose exceeding 10 mg of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.\n* Known additional malignancy that is progressing or has required active treatment within the past 2 years.\n* Has known active CNS metastases and\u002For carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention. Has severe hypersensitivity (≥ grade 3) to pembrolizumab and\u002For any of its excipients.\n* Has severe hypersensitivity (≥ grade 3) to pembrolizumab and\u002For any of its excipients.\n* Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid allowed).\n* Has a history of (non-infectious) pneumonitis\u002Finterstitial lung disease that required steroids or has current pneumonitis\u002Finterstitial lung disease.\n* Has an active infection requiring systemic therapy.\n* Has not adequately recovered from major surgery or has ongoing surgical complications.\n* Has a history or current evidence of any condition, therapy, or laboratory abnormality or other circumstance that might confound the results of the study, interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.\n* Patients with pathologically confirmed Hodgkin-like RT (RT-classical Hodgkin's lymphoma \\[cHL\\]).\n* Estimated life expectancy of \\\u003C 1 month as determined by the treating investigator.\n* Uncontrolled active illness including but not limited to heart failure, unstable ischemic heart disease, arrhythmia, psychiatric illness, acute renal failure, and any other conditions that would reasonably be expected to limit compliance with the study protocol.\n* Concurrent active Hepatitis B (defined as HBsAg positive and\u002For detectable HBV deoxyribonucleic acid \\[DNA\\]) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection.\n* Corrected QT interval (QTc) prolongation (defined as a Fridericia's corrected QT \\[QTcF\\] \\> 450 msecs) or other significant electrocardiogram (ECG) abnormalities including second degree atrioventricular (AV) block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats\u002Fmin).\n* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.\n* Unwilling or unable to follow protocol requirements.\n* Received any other investigational agent within 30 days prior to enrollment.\n* HIV-infected participants with a history of Kaposi's sarcoma and\u002For multicentric Castleman's disease.\n* History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding.NOTE: Patients on active anti-coagulation, anti-platelet therapies, and other medications that may increase bleeding risks may be allowed on study, permitted that these potentially interacting drugs may be safely held in the setting of thrombocytopenia, and at the discretion of the treating investigator and with close monitoring.\n* Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.\n* Has had an allogeneic tissue\u002Fsolid organ transplant. Note: Patients with prior allogeneic hematopoietic stem cell transplant or allogeneic cellular therapy are allowed, provided they meet they meet the washout period.\n* Use of medications that are strong CYP3A4 inhibitors or inducers or P-gp and\u002For BCRP substrates with a narrow therapeutic index within 14 days prior to first dose of study treatment or 5 half-lives of the given drug, whichever is longer",{"count":75,"type":21},32,[24],"This phase II trial tests how well nemtabrutinib in combination with pembrolizumab works in treating patients with Richter transformation, diffuse large B-cell lymphoma subtype (RT-DLBCL). Nemtabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cells (a type of white blood cell) in cancers such as Richter transformation at abnormal levels. This may help keep cancer cells from growing and spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Giving nemtabrutinib in combination with pembrolizumab may kill more cancer cells in patients with RT-DLBCL.",[27,79,80],"Diffuse Large B-Cell Lymphoma","Chronic Lymphocytic Leukemia","2026-05-19",{"date":83,"type":32},"2026-05-20",{"date":85,"type":21},"2026-06-15",{"date":87,"type":21},"2030-06-01",{"name":89,"class":39},"Roswell Park Cancer Institute",1,{"id":92,"slug":93,"hasResults":11,"nctId":94,"briefTitle":95,"officialTitle":96,"acronym":4,"eligibilityCriteria":97,"healthyVolunteers":11,"sex":17,"minAge":98,"maxAge":99,"enrollmentInfo":100,"targetDuration":4,"studyType":22,"phases":102,"briefSummary":104,"conditions":105,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":114,"lastUpdatePostDateStruct":115,"startDateStruct":117,"completionDateStruct":119,"leadSponsor":121,"locationsCount":90},"100400218","phase-1-autologous-stem-cell-transplant-followed-by-polatuzumab-vedotin-in-patients-with-b-cell-non-hodgkin-and-hodgkin-lymphoma-100400218","NCT04491370","Autologous Stem Cell Transplant Followed by Polatuzumab Vedotin in Patients With B-cell Non-Hodgkin and Hodgkin Lymphoma","Safety and Tolerability of Myeloablative Conditioning and Autologous Stem Cell Transplantation Followed by Polatuzumab Vedotin (PV) Immunoconjugate Therapy in Patients With B-cell Non-Hodgkin and Hodgkin Lymphoma","Inclusion Criteria:\n\n* Diagnosis B-cell NHL: Burkitt lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, Transformed Follicular Lymphoma, Richter syndrome, and CD20+ Hodgkin Lymphoma.\n* Disease Status Primary Induction Failure, 1st, 2nd or 3rd relapse\u002Fprogression having attained a CR, PR, or stable disease post reinduction therapy.\n* Performance Level Patients must have a performance status ≥ 50%. Use Karnofsky for patients \\> 16 years of age and Lansky for patients less than or equal to 16 years of age. See Appendix I for performance score.\n* Life Expectancy Patients must have a life expectancy of \\> 6 weeks.\n* Prior Therapy Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.\n\n  1. Myelosuppressive chemotherapy: Must not have received within 2 weeks of entry onto this study (4 weeks if prior nitrosourea).\n  2. Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with a biologic agent.\n* Organ Function Requirements\n\nAdequate Renal Function Defined As:\n\n* Creatinine clearance or radioisotope GFR \\> 60 mL\u002Fmin\u002F1.73 m2 or\n* A serum creatinine based on age\u002Fgender as follows:\n\nAge Maximum Serum Creatinine (mg\u002FdL) Male Female\n\n* 12 to \\\u003C 13 years 1.2 1.2 13 to \\\u003C 16 years 1.5 1.4\n* 16 years 1.7 1.4\n\n  * Adequate Liver Function Defined As:\n\n    * Total bilirubin less than or equal to 1.5 x upper limit of normal (ULN) for age, and\n    * SGOT (AST) or SGPT (ALT) \\\u003C 3 x upper limit of normal (ULN) for age for presumed hepatic leukemia or lymphoma.\n  * Adequate Cardiac Function Defined As:\n\n    * Shortening fraction of \\> 27% by echocardiogram, or\n    * Ejection fraction of \\> 50% by radionuclide angiogram.\n  * Adequate Pulmonary Function Defined As:\n\n    • Normal respiratory rate for age and a pulse oximetry \\> 94% on room air unless due to underlying malignancy.\n  * Peripheral Blood Stem Cell Collection\n\n    • Patients have a target of 5.0 x 106 CD34 (minimum of 2.5 x 106 CD34) PBSC collected and cryopreserved prior to start of myeloablative conditioning\n  * All patients and\u002For their parents or legal guardians must sign a written informed consent.\n\nExclusion Criteria:\n\n* Patient may not have had a prior stem cell transplant\n* Patients must not have active CNS lymphoma\n* Other concurrent investigational agents for treatment of B-cell lymphoma\n* Pregnancy and\u002For active Breast Feeding\n* Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation.\n* Patient must not have an uncontrolled infection.\n* Patient must not have ≥ Grade 3 neuropathy.","12 Years","70 Years",{"count":101,"type":21},20,[103,24],"PHASE1","Patients will receive one of two conditioning regimens (BEAM or CBV) before receiving an autologous stem cell transplant (ASCT). If patients achieve either complete, partial, or stable response following ASCT, they will receive an IV dose of Polatuzumab Vedotin once every 21 days until they receive 8 doses. After Polatuzumab Vedotin therapy is completed, patients will be followed every 4 months for about 2 years.",[106,107,108,109,110,111,112,27,113],"B-cell Lymphoma","Burkitt Lymphoma","Diffuse Large B Cell Lymphoma","Follicular Lymphoma","Mantle Cell Lymphoma","Marginal Zone Lymphoma","Transformed Non-Hodgkin Lymphoma","Hodgkin Lymphoma","2026-04-10",{"date":116,"type":32},"2026-04-15",{"date":118,"type":32},"2021-08-01",{"date":120,"type":21},"2027-08-15",{"name":122,"class":39},"New York Medical College",{"id":124,"slug":125,"hasResults":11,"nctId":126,"briefTitle":127,"officialTitle":128,"acronym":4,"eligibilityCriteria":129,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":130,"targetDuration":4,"studyType":22,"phases":132,"briefSummary":133,"conditions":134,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":136,"lastUpdatePostDateStruct":137,"startDateStruct":139,"completionDateStruct":141,"leadSponsor":143,"locationsCount":145},"100469069","phase-2-acalabrutinib-venetoclax-and-durvalumab-for-the-treatment-of-richter-transformation-from-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma-100469069","NCT05388006","Acalabrutinib, Venetoclax and Durvalumab for the Treatment of Richter Transformation From Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma","MC198B, Phase II Study of a Combination Therapy of Acalabrutinib, Venetoclax and Durvalumab in Patients With Richter Transformation From Chronic Lymphocytic Leukemia (CLL)","Inclusion Criteria:\n\n* Age \\>= 18 years willing to provide consent and follow-up\n* Diagnosis of CLL according to the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2018 criteria (Hallek et al., 2018) or small lymphocytic lymphoma (SLL) according to the World Health Organization (WHO) 2008 criteria (Harris, 1999). This includes previous documentation of:\n\n  * Biopsy-proven SLL according to WHO 2008 criteria, or\n  * Diagnosis of CLL according to IWCLL 2018 criteria as evidenced by all of the following:\n\n    * Peripheral blood B cell count of \\>= 5 x 10\\^9\u002FL consisting of small to moderate size lymphocytes (If there are enough evidence to document the prior diagnosis of CLL, it is not required to meet the criteria of peripheral blood B cell count more than 5 x 10\\^9\u002FL )\n    * Immunophenotyping consistent with CLL defined as:\n\n      * The predominant population of lymphocytes share both B-cell antigens (CD19, CD20 \\[typically dim expression\\], or CD23) as well as CD5 in the absence of other pan-T-cell markers (CD3, CD2, etc.)\n      * Clonality as evidenced by kappa or lambda light chain expression (typically dim immunoglobulin expression) or other genetic method (e.g. immunoglobulin heavy chain variable \\[IGHV\\] analysis)\n\n        * NOTE: Splenomegaly, hepatomegaly, or lymphadenopathy are not required for the diagnosis of CLL\n    * Before diagnosing CLL or SLL, mantle cell lymphoma must be excluded by demonstrating a negative fluorescence in situ hybridization (FISH) analysis for t(11;14)(IgH\u002FCCND1) on peripheral blood or tissue biopsy or negative immunohistochemical stains for cyclin D1 on involved tissue biopsy\n    * If prior CLL diagnosis was confirmed, or CLL diagnosis was confirmed on bone marrow examination or tissue biopsy, peripheral blood B cell count less than 5 x 10\\^9\u002FL is allowed\n* Biopsy proven Richter's transformation of the CLL\n\n  * NOTE: Previously treated patients including CLL therapy can be enrolled. If Richter's transformation (RT) developed from prior untreated CLL and has not received any RT directed therapy, then patient is not eligible\n* Richter patients with prior or concurrent CLL diagnosis and do not have other option for standard therapy per treating physician's discretion\n* Measurable disease can be detected in positron emission tomography (PET) or computed tomography (CT) (\\>= 1 cm in diameter)\n* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2\n* Absolute neutrophil count \\>= 0.7 x 10\\^9\u002FL unless marrow was involved by CLL or RT, then absolute neutrophil count (ANC) \\>= 0.3 x 10\\^9\u002FL (=\\\u003C 14 days prior to registration)\n* Platelet count \\>= 40 x 10\\^9\u002FL unless marrow was involved by CLL or RT, then platelet \\>= 30 x 10\\^9\u002FL without transfusion =\\\u003C 1 week prior to study registration (=\\\u003C 14 days prior to registration)\n* Hemoglobin (Hgb) \\>= 8 unless marrow was involved by CLL or RT, then Hgb \\>= 7 without transfusion =\\\u003C 1 week prior to study registration (=\\\u003C 14 days prior to registration)\n* Total bilirubin =\\\u003C 1.5 x upper limit of normal (ULN) unless due to confirmed Gilbert's disease (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician (=\\\u003C 14 days prior to registration)\n\n  * Note: If total bilirubin is \\> 1.5 x ULN, a direct bilirubin should be performed and must be =\\\u003C upper limit of normal\n* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \\[SGOT\\]) or alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \\[SGPT\\]) =\\\u003C 2.5 X ULN unless liver metastases are present, in which case it must be =\\\u003C 5 x ULN (=\\\u003C 14 days prior to registration)\n* Calculated creatinine clearance of \\> 30 mL\u002Fmin by the Cockcroft-Gault formula (Cockcroft and Gault 1976) (=\\\u003C 14 days prior to registration)\n* Negative pregnancy test done =\\\u003C 7 days prior to registration, for women of childbearing potential only\n\n  * NOTE: The following restrictions apply while the patient is receiving study treatment and for the specified times before and after:\n\n    * Female patient of child-bearing potential\n\n      * Female patients of childbearing potential who are not abstinent and intend to be sexually active with a non sterilized male partner must use at least 1 highly effective method of contraception from the time of screening throughout the total duration of the drug treatment and the drug washout period (180 days after the last dose of study treatment). Non-sterilized male partners of a female patient of childbearing potential must use male condom plus spermicide throughout this period. Cessation of birth control after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Female patients should also refrain from breastfeeding throughout this period\n    * Male patients with a female partner of childbearing potential\n\n      * Non-sterilized male patients who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use a male condom plus spermicide from the time of screening throughout the total duration of the drug treatment and the drug washout period (180 days after the last dose of study treatment). However, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Male patients should refrain from sperm donation throughout this period\n    * Female partners (of childbearing potential) of male patients must also use a highly effective method of contraception throughout this period\n    * Females of childbearing potential are defined as those who are not surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy) or post-menopausal\n    * Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:\n\n      * Women \\\u003C 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution\n      * Women \\>= 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \\> 1 year ago, had chemotherapy-induced menopause with last menses \\> 1 year ago\n    * Highly effective methods of contraception, defined as one that results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly are described below. Note that some contraception methods are not considered highly effective (e.g. male or female condom with or without spermicide; female cap, diaphragm, or sponge with or without spermicide; non-copper containing intrauterine device; progestogen-only oral hormonal contraceptive pills where inhibition of ovulation is not the primary mode of action \\[excluding Cerazette\u002Fdesogestrel which is considered highly effective\\]; and triphasic combined oral contraceptive pills)\n    * Effective methods include:\n\n      * Copper T intrauterine device\n      * Levonorgestrel-releasing intrauterine system (e.g., Mirena)\n      * Implants: Etonogestrel-releasing implants: e.g. Implanon or Norplant\n      * Intravaginal: Ethinylestradiol\u002Fetonogestrel-releasing intravaginal devices: e.g. NuvaRing\n      * Injection: Medroxyprogesterone injection: e.g. Depo-Provera\n      * Combined pill: Normal and low dose combined oral contraceptive pill\n      * Patch: Norelgestromin\u002Fethinylestradiol-releasing transdermal system: e.g. Ortho Evra\n      * Minipill: Progesterone based oral contraceptive pill using desogestrel: Cerazette is currently the only highly effective progesterone-based\n      * Tubal ligation\n* Provide informed written consent\n* Willing to return to enrolling institution for follow-up\n* Willing to provide tissue, blood, and bone marrow samples for mandatory correlative research purposes\n\nExclusion Criteria:\n\n* Any of the following uncontrolled intercurrent illness:\n\n  * Clinically significant cardiovascular disease such as:\n\n    * Symptomatic arrhythmias\n    * Congestive heart failure\n    * Myocardial infarction =\\\u003C 3 months prior to registration\n    * Any class 3 or 4 cardiac disease as defined by the New York Heart Association functional classification\n    * Uncontrolled hypertension\n    * Unstable angina pectoris\n\n      * Note: Subjects with controlled, asymptomatic atrial fibrillation can enroll on study\n  * Serious chronic gastrointestinal conditions associated with diarrhea\n  * History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)\n  * History of stroke or intracranial hemorrhage within 6 months before first dose of study drug\n  * History of bleeding diathesis (e.g., hemophilia, von Willebrand disease)\n  * Active uncontrolled infection (e.g., bacterial, viral or fungal, including subjects with positive cytomegalovirus \\[CMV\\] deoxyribonucleic acid \\[DNA\\] polymerase chain reaction \\[PCR\\]) requiring systemic therapy. NOTE: When the infection is controlled with systemic therapy, patients are permitted for this study\n  * Active tuberculosis infection (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis \\[TB\\] testing in line with local practice)\n  * Known human immunodeficiency virus (HIV\u002Facquired immunodeficiency syndrome \\[AIDS\\]) infection as further severe immunosuppression with this regimen may occur\n  * Hepatitis B or C serologic status:\n\n    * Hepatitis B surface antigen and hepatitis B PCR positive will be excluded\n    * Hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative, and hepatitis B PCR positive will be excluded\n    * These above patients once treated for hepatitis B and became hepatitis B PCR negative, they will be eligible\n    * Hepatitis C PCR positive will be excluded. Once treated and hepatitis C PCR negative will be eligible\n    * NOTE: Once patients with active hepatitis treated with effective therapy and adequate disease control, they will be allowed for participation\n* Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown\n\n  * Pregnant women\n  * Nursing women\n  * Men and women of childbearing potential who are unwilling to employ highly effective method of contraception starting with the screening visit through 180 days after the last dose of trial treatment\n* Treated with other active investigational agents (excluding venetoclax, acalabrutinib. or ibrutinib) =\\\u003C 5 half -lives of the previous investigational agents, please consult study chair for the specific investigational agent\n* Prior durvalumab treatment. Note: If patients were treated with other prior PD1 blockade or PDL1 blockade, they will still be eligible\n* Active or recent (=\\\u003C 2 months) documented autoimmune or inflammatory disorders (including inflammatory bowel disease \\[e.g., colitis or Crohn's disease\\], diverticulitis \\[with the exception of diverticulosis\\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \\[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\\]) not being controlled. Exceptions:\n\n  * Patients with vitiligo or alopecia\n  * Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement\n  * Any chronic skin condition that does not require systemic therapy\n  * Patients without active disease in the last 3 years may be included but only after consultation with the study physician\n  * Patients with celiac disease controlled by diet alone\n* Evidence of interstitial lung disease or active, non-infectious pneumonitis\n* Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial\n* Active central nervous system (CNS) lymphoma or cerebrospinal fluid involvement with malignant lymphoma cells that requires therapy\n* Clinically significant coagulopathy per investigator's assessment (stable anticoagulation except warfarin or other vitamin K antagonist will be allowed)\n* Received an allogenic stem cell transplant within the last 2 years; Or prior history of allogeneic stem cell transplant with history of graft versus host disease (GVHD)\n* Active chronic GVHD requiring treatment\n* Chronically taking a strong CYP3A inhibitor or inducer and moderate inducer and cannot be switched to an alternative agent at least 4 days prior to trial therapy initiation that in the opinion of investigator\u002Ftreating physicians precludes utilization of trial therapy\n* Patients taking proton pump inhibitor will be excluded. NOTE: Patient may be switch to an H2 blocker or antiacid\n* History of another primary malignancy except for:\n\n  * Malignancy treated with curative intent and with no known active disease \\>= 5 years before the first dose of study drug and of low potential risk for recurrence\n  * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease\n  * Adequately treated carcinoma in situ without evidence of disease\n  * Indolent malignancy with expected life expectancy more than 2 years\n* Current or prior use of immunosuppressive medication =\\\u003C 5 half-lives of previous immunosuppressive medication. Note: Immunosuppressive medication is in reference to treatment of autoimmune or inflammatory disorders (e.g., with cyclosporine, tacrolimus, methotrexate, azathioprine) due to the potential suppressive effect on T-cells. Prior treatments administered as CLL- or lymphoma-directed treatment are not considered immunosuppressive medication under this criterion, as clarified below. The following are exceptions to this criterion:\n\n  * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)\n  * Systemic corticosteroids at physiologic doses not to exceed =\\\u003C 30 mg\u002Fday of prednisone or its equivalent\n  * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)\n  * Receipt of live attenuated vaccine =\\\u003C 30 days prior to registration. Note: Patients, if enrolled, should not receive live vaccine whilst receiving investigational product (IP) and up to 30 days after the last dose of IP\n  * Received monoclonal antibody therapy for CLL or lymphoma \\> 7 days prior to registration\n  * Received a chimeric antigen receptor T-cell therapy for CLL or lymphoma \\> 30 days prior to registration\n  * Received bi-specific antibody therapy for CLL or lymphoma \\> 7 days prior to registration\n  * Consult with the study chair if other specific medication in question\n* Any radiation therapy =\\\u003C 1 week prior to registration\n* Any major surgery =\\\u003C 28 days prior to registration (Note: Routine tissue or nodal biopsy or small procedures typically heal fast will not be counted as surgery)\n* Body weight =\\\u003C 30 kg\n* Life expectancy \\\u003C 12 weeks",{"count":131,"type":21},27,[24],"This phase II trial tests whether acalabrutinib, venetoclax, and durvalumab work in treating patients with Richter transformation from chronic lymphocytic leukemia or small lymphocytic lymphoma. Richter transformation is a rare condition in which chronic lymphocytic leukemia or small lymphocytic lymphoma changes into a fast-growing type of lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving acalabrutinib, venetoclax, and durvalumab may help improve survival in patients with Richter transformation.",[80,27,135],"Small Lymphocytic Lymphoma","2026-03-23",{"date":138,"type":32},"2026-03-25",{"date":140,"type":32},"2023-01-05",{"date":142,"type":21},"2027-02-22",{"name":144,"class":39},"Mayo Clinic",3,{"id":147,"slug":148,"hasResults":11,"nctId":149,"briefTitle":150,"officialTitle":151,"acronym":4,"eligibilityCriteria":152,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":153,"targetDuration":4,"studyType":22,"phases":154,"briefSummary":155,"conditions":156,"keywords":157,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":161,"lastUpdatePostDateStruct":162,"startDateStruct":164,"completionDateStruct":166,"leadSponsor":168,"locationsCount":170},"100414622","phase-2-polatuzumab-vedotin-in-combination-with-chemotherapy-in-subjects-with-richters-transformation-100414622","NCT04679012","Polatuzumab Vedotin in Combination With Chemotherapy in Subjects With Richter's Transformation","Phase II Study of Polatuzumab Vedotin in Combination With Chemotherapy in Subjects With Richter's Transformation","Inclusion Criteria:\n\n* Subject must have confirmed diagnosis of CLL or small lymphocytic lymphoma (SLL) based upon 2018 International Workshop on CLL (IwCLL) criteria, with biopsy proven Richter's Transformation to a DLBCL subtype.\n* Subject must be ≥18 years of age.\n* Subject must be able to sign informed consent\n* Ability and willingness to comply with the study protocol procedures\n* Life expectancy of at least 24 weeks\n* Subject must have an Eastern Cooperative Oncology Group performance status of ≤2.\n* Subject must have measurable disease with atleast on LN\\>- 1.5cm in longest diameter\n* Subject must have adequate bone marrow function and meet the below thresholds prior to treatment.\n\n  * Absolute neutrophil count of ≥1000 cell\u002FuL\n  * Hemoglobin ≥ 7 g\u002FdL\n  * Platelet count ≥ 30,000 cells\u002FuL- Subjects may receive growth factor or transfusion support no less than 7 days prior to enrollment or C1 D1.\n* Subject must have adequate organ function and meet the thresholds below:\n\n  * Total bilirubin ≤ 1.5 times the upper limit of normal (ULN). Subjects with Gilbert's disease will be granted exception to this rule.\n  * Creatinine clearance \\>30 ml\u002Fmin\u002F1.73m2 as calculated by the MDRD equation.\n  * Ejection fraction ≥ 50% measured by transthoracic echocardiogram or MUGA scan\n* For women of childbearing potential: agreement to remain abstinent or use of contraceptive methods that result in a failure rate of \\\u003C 1% per year during the treatment period and for at least 12 months after the last dose of study drug.\n\n  * A woman is considered to be of childbearing potential if she is post-menarcheal, has not reached a postmenopausal state (i.e. ≥ 12 months of amenorrhea with no identified cause other than menopause) and has not undergone surgical sterilization (removal of ovaries and or uterus)\n\n    * Acceptable forms of contraception are bilateral tubal ligation, male sterilization, or copper intrauterine devices.\n  * For women considered to have childbearing potential a negative serum pregnancy test within 7 days prior to study enrollment and dosing is required.\n* For men, agreement to remain abstinent, or to use a condom plus an additional contraceptive method during the treatment period and for at least 5 months after the last dose of study drug.\n\n  * Men must agree not to donate sperm during that period of time. Male patients interested in preservation of fertility should be advised to sperm bank prior to enrollment and treatment initiation.\n\nExclusion Criteria:\n\n* Diagnosis of Richter's Transformation not of DLBCL subtype (including but not limited to Hodgkin lymphoma, PLL)\n* Prior therapy targeting Richter's transformation.\n* Any subject that initiates a targeted agent such as BTKi, venetoclax, or PI3K prior to enrollment (Continuation of a targeted CLL directed therapy such as a BTKi, venetoclax, or PI3K will be permitted as a bridge through screening but add on therapies or change in therapy will be exclusionary. These continuation therapies will be permitted up 72 hours prior to study initiation. Bridging therapy with steroid up to equivalent of 40mg of Dexamethasone daily will be allowed prior to study treatment and can be continued up to 24 hours prior to study treatment)\n* Subject has undergone an allogeneic stem cell transplant for CLL within 6 months of study entry.\n* Subject has an active or presumed secondary malignancy at time of enrollment. A subject will be eligible if a previous malignancy was treated with curative intent and there is no evidence of disease recurrence for the past 3 years. Non-melanomatous and cervical squamous cell cancers are an exception and if excised will be allowed to enroll regardless of timing of excision.\n* Subject is known to be positive for HIV.\n* Active hepatitis C or hepatitis B defined by positive PCRs for viral DNA\u002FRNA. Subjects with a positive Hep B core antibody and negative PCR, are allowed to enroll (prophylaxis is strongly encouraged and monthly monitoring of Hep B PCR is mandatory).\n* Subject has baseline ≥ Grade 2 or greater peripheral neuropathy.\n* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies\n* Clinical evidence or known central nervous system involvement with transformed large cells\n* Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results\n* Significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, congestive heart failure, myocardial infarction within the previous 6 months, unstable arrhythmias, or unstable angina)\n* Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment or any major episode of infection requiring treatment with intravenous antibiotics or hospitalization within 4 weeks before Cycle 1 day 1.\n* Major surgery within 4 weeks before the start of Cycle 1 day 1. Superficial lymph node biopsies or laprascopic lymph node biopsies are exclusionary to this rule.",{"count":101,"type":21},[24],"This study evaluates the effectiveness and safety of Polatuzumab vedotin plus infusional chemoimmunotherapy containing rituximab, etoposide, prednisone, cyclophosphamide and hydroxydaunorubicin. This is a single arm study. Enrolled patients will receive up to six cycles (21-day cycles) of therapy. While on study, subjects will be monitored weekly until end of treatment, then followed for 52 weeks or until disease progression or discontinuation due to toxicity or death. After completion of the 52-week follow-up\u002FEnd of study visit, Subjects will be followed for an additional 104 week period, with an assessment occurring every 12 weeks to evaluate survival outcomes and next line of treatments only.",[27,80],[158,159,160],"Polatuzumab vedotin","CLL","Richter's Transformation","2025-10-01",{"date":163,"type":32},"2025-10-07",{"date":165,"type":32},"2021-09-24",{"date":167,"type":21},"2027-09",{"name":169,"class":39},"Weill Medical College of Cornell University",4,{"id":172,"slug":173,"hasResults":11,"nctId":174,"briefTitle":175,"officialTitle":176,"acronym":4,"eligibilityCriteria":177,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":178,"targetDuration":4,"studyType":22,"phases":179,"briefSummary":180,"conditions":181,"keywords":4,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":184,"lastUpdatePostDateStruct":185,"startDateStruct":187,"completionDateStruct":189,"leadSponsor":191,"locationsCount":90},"100572622","phase-1-zanubrutinib-in-combination-with-odronextamab-for-the-treatment-of-patients-with-richters-transformation-100572622","NCT06735664","Zanubrutinib in Combination With Odronextamab for the Treatment of Patients With Richter's Transformation","A Phase I Study of Covalent BTK Inhibitor Zanubrutinib in Combination With a CD3-CD20 Bispecific Antibody Odronextamab in Patients With Richter's Transformation","Inclusion Criteria:\n\n* Documented informed consent of the participant and\u002For legally authorized representative\n\n  * Assent, when appropriate, will be obtained per institutional guidelines\n* Age: ≥ 18 years\n* Eastern Cooperative Oncology Group (ECOG) ≤ 2\n* Histologically confirmed diagnosis of Richter transformation (RT; transformed CLL). Only patients who have diffuse large B-cell lymphoma histology in transformation are eligible (for example, patients with transformation into Hodgkin lymphoma subtype are not eligible)\n* Evidence of CD20 positivity at screening (by immunohistochemistry \\[IHC\\] or flow cytometry)\n* Treatment naïve or relapsed\u002F refractory disease. Patients with either previously untreated RT and previously treated RT are eligible, regardless of whether or not they had received CLL-directed therapy\n* Radiographically measurable lymphadenopathy (≥ 1.5 cm) or splenomegaly, or bone marrow involvement by diffuse large B cell lymphoma (DLBCL)\u002FRT\n* Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy\n* Without bone marrow involvement: Absolute neutrophil count (ANC) ≥ 1,000\u002Fmm\\^3\n\n  * NOTE: A participant may not have received granulocyte colony stimulating factor (G-CSF) within 3 days of first dose of the assigned study treatment in order to meet this eligibility requirement\n* With bone marrow involvement: ANC ≥ 500\u002Fmm\\^3\n\n  * NOTE: A participant may not have received granulocyte colony stimulating factor (G-CSF) within 3 days of first dose of the assigned study treatment in order to meet this eligibility requirement\n* Without bone marrow involvement: Platelets ≥ 50,000\u002Fmm\\^3\n\n  * NOTE: A participant may not have received platelet transfusion within 7 days of first dose of the assigned study treatment in order to meet this eligibility requirements\n* With bone marrow involvement: Platelets ≥ 25,000\u002Fmm\\^3\n\n  * NOTE: A participant may not have received platelet transfusion within 7 days of first dose of the assigned study treatment in order to meet this eligibility requirements\n* With bone marrow involvement: Hemoglobin (Hgb) ≥ 7 g\u002FdL\n* Total bilirubin ≤ 2 x upper limit of normal (ULN) or ≤ 3 x ULN for Gilbert's disease or compensated hemolysis directly attributable to CLL\n* Aspartate aminotransferase (AST) ≤ 3 x ULN\n* Alanine aminotransferase (ALT) ≤ 3 x ULN\n* Alkaline phosphatase (ALP) ≤ 2.5 x ULN or ≤ 5 x ULN if attributed to lymphoma involvement of the liver\n* Serum creatinine ≤ 1.5 x ULN OR creatinine clearance of ≥ 50 mL\u002Fmin per 24 hour urine test or the Cockcroft-Gault formula\n* If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) ≤ 1.5 x ULN\n* If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants\n* If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN\n* If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants\n* Left ventricular ejection fraction (LVEF) ≥ 45%\n\n  * Note: To be performed within 28 days prior to day 1 of protocol therapy\n* Seronegative for hepatitis C virus (HCV), hepatitis B virus (HBV) (surface antigen negative) and no history of HIV OR\n\n  * If seropositive for HBV or HCV, nucleic acid quantitation must be performed. Viral load must be undetectable\n  * HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial\n* Women of childbearing potential (WOCBP): Negative serum pregnancy test\n* Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of study therapy. Sperm donation is prohibited during the study and for 6 months after the last dose of the assigned study treatment. Highly effective contraceptive measures include:\n\n  * Stable use of combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal) or progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation initiated ≥ 2 menstrual cycles prior to screening\n  * Intrauterine device (IUD); intrauterine hormone-releasing system (IUS)\n  * Bilateral tubal ligation\u002Focclusion\n  * Vasectomized partner (provided that the male vasectomized partner is the sole sexual partner of the study patient and that the partner has obtained medical assessment of surgical success for the procedure)\n  * Sexual abstinence, only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study drugs\n  * Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for \\> 1 year (women only)\n  * A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient to determine the occurrence of a postmenopausal state. The above definitions are according to the clinical trial facilitation group guidance. Pregnancy testing and contraception are not required\n\nExclusion Criteria:\n\n* Allogeneic bone marrow or organ transplant within 6 months or evidence of active graft versus host diseae (GVHD)\n* Prior CD20-targeted bispecific antibody therapy\n* Chronic systemic corticosteroid use \\> 10 mg\u002Fday of prednisone or equivalent within 72 hours (h) of start of study treatment. Patients who received corticosteroid treatment with ≤ 10 mg\u002Fday of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks' duration prior to day 1 of cycle 1. Patients may have received a brief (≤ 10 days) course of systemic steroids (≤ 80 mg prednisone equivalent per day) up to 24 hours prior to initiation of study therapy for control of lymphoma-related symptoms\n* Therapeutic anticancer antibodies within 2 weeks prior to day 1 of protocol therapy\n* Radio- or toxin-immunoconjugates within 10 weeks prior to day 1 of protocol therapy\n* Live vaccine within 28 days prior to day 1 of protocol therapy\n* Any investigational therapy within 28 days or 5 half-lives of the drug, whichever is shorter, prior to the start of study treatment\n* Standard radiotherapy within 14 days of first administration of study treatment\n* Prior organ transplantation\n* Chemotherapy, within 2 weeks prior to day 1 of protocol therapy; targeted therapy within 6 half-lives or two weeks, whichever is shorter\n* Requires treatment with a strong CYP3A4 inducers\u002F inhibitor while on protocol therapy\n* Uncontrolled immune hemolysis or thrombocytopenia\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drug\n* Known hypersensitivity to both allopurinol and rasburicase\n* Unstable cardiac disease as defined by one of the following:\n\n  * Cardiac events such as myocardial infarction (MI) within the past 6 months\n  * NYHA (New York Heart Association) heart failure class III-IV\n  * Uncontrolled atrial fibrillation or hypertension\n* Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before the start of study treatment\n* Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)\n* Active uncontrolled cardiac arrythmia\n* History or concurrent condition of interstitial lung disease and\u002For severely impaired lung function\n* Evidence of central nervous system (CNS) involvement within 6 months prior to initiation of study therapy\n* Major surgery (under general anesthesia) within 30 days prior to day 1 of protocol therapy\n* Clinically significant uncontrolled illness\n* Evidence of any active infection (bacterial, viral, fungal, mycobacterial, parasitic or other) at study enrollment or within 2 weeks of study enrollment, if requiring ongoing treatment and\u002For has the potential to cause disseminated disease or severe infection upon immunosuppression. There should be evidence that the infection has cleared or is well controlled by start of study therapy\n* Active COVID-19 infection\n* Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV)\n\n  * NOTE: Participants with HIV who have controlled infection (undetectable viral load and CD4 count above 350 cells\u002FuL either spontaneously or on a stable antiviral regimen) are permitted\n  * NOTE: Participants who are hepatitis B surface antigen positive or who are hepatitis B core antibody positive should undergo evaluation by a specialist and be considered to have controlled infection (serum hepatitis B virus deoxyribonucleic acid \\[DNA\\] polymerase chain reaction \\[PCR\\] that is below the limit of detection AND receiving anti-viral therapy for hepatitis B) before they are permitted onto study\n  * NOTE: Participants who are HCV antibody positive who have controlled infection (undetectable HCV ribonucleic acid \\[RNA\\] by PCR either spontaneously or in response to a successful prior course of anti-HCV therapy) are permitted\n* Cytomegalovirus (CMV) infection as noted by detectable levels on peripheral blood polymerase chain reaction (PCR) assay. Patients who show detectable levels of CMV at screening will need to be treated with appropriate antiviral therapy and demonstrate at least 2 undetectable levels of CMV by PCR assay (at least 7 days apart) before being re-considered for eligibility\n* Other active malignancy. Patients with a prior (in the past 5 years) 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. History of the following is allowed:\n\n  * Malignancy treated with curative intent and no known active disease present for ≥ 2 years prior to initiation of therapy on current study\n  * Adequately treated non-melanoma skin cancer or lentigo maligna (melanoma in situ) without evidence of disease\n  * Adequately treated in situ carcinomas (e.g., cervical, esophageal, etc.) without evidence of disease\n  * Asymptomatic prostate cancer managed with \"watch and wait\" strategy\n* Females only: Pregnant or breastfeeding\n* Inability to swallow and retain oral medication\n* Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures\n* Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility\u002Flogistics)",{"count":40,"type":21},[103],"This phase I trial tests the safety and side effects of zanubrutinib in combination with odronextamab and how well it works in treating patients with Richter's transformation. Zanubrutinib, a tyrosine kinase inhibitor, blocks a protein called Bruton tyrosine kinase (BTK), which may help keep cancer cells from growing. Odronextamab is a bispecific monoclonal antibody that can bind to two different antigens at the same time. Odronextamab binds to CD20 found on B-cells (a type of white blood cell) and on many B-cell cancers and to CD3 on T-cells (also a type of white blood cell) and may interfere with the ability of cancer cells to grow and spread. Giving zanubrutinib in combination with odronextamab may be safe, tolerable and\u002For effective in treating patients with Richter's transformation.",[182,183,27,54],"Recurrent Transformed Chronic Lymphocytic Leukemia","Refractory Transformed Chronic Lymphocytic Leukemia","2025-09-14",{"date":186,"type":32},"2025-09-16",{"date":188,"type":32},"2025-08-14",{"date":190,"type":21},"2027-12-13",{"name":192,"class":39},"City of Hope Medical Center",{"id":194,"slug":195,"hasResults":11,"nctId":196,"briefTitle":197,"officialTitle":197,"acronym":198,"eligibilityCriteria":199,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":200,"enrollmentInfo":201,"targetDuration":4,"studyType":22,"phases":203,"briefSummary":204,"conditions":205,"keywords":206,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":207,"lastUpdatePostDateStruct":208,"startDateStruct":210,"completionDateStruct":212,"leadSponsor":214,"locationsCount":216},"100587270","phase-2-chop-plus-mosunetuzumab-as-first-line-in-patients-with-richters-syndrome-a-phase-ii-study-of-the-spanish-group-of-cll-100587270","NCT06926205","CHOP Plus Mosunetuzumab as First Line in Patients With Richter´s Syndrome: a Phase II Study of the Spanish Group of CLL","GELLC9RICHTER","Inclusion Criteria:\n\n1. Capable of giving signed informed consent as described in Section 13.2, which includes compliance with the requirements and restrictions listed in the Informed Consent Form and this protocol.\n2. Aged between 18 and 79 years at the time of signing the Informed Consent Form\n3. Ability to comply with the study protocol and procedures and required hospitalizations, in the investigator's judgement.\n4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2.\n5. Adult patients with previously untreated, histologically proven Richter's syndrome, diffuse large B cell variants, following WHO 2008 criteria (Swerdlow SH, 2008).\n6. Screening flow cytometry or immunohistochemistry (IHC) evidence of CD20 positive disease as per central review (dim expression of CD20 is acceptable)\n7. Adequate BM function independent of growth factor or transfusion at screening as follows unless cytopenia is clearly due to marrow involvement of CLL:\n\n   1. Platelet count ≥75 x 109\u002FL; in cases of thrombocytopenia clearly due to marrow involvement of CLL (per the discretion of the investigator), platelet count should be ≥ 30 x 109\u002FL.\n   2. ANC ≥1 x 109\u002FL unless neutropenia is clearly due to marrow involvement of CLL (per the discretion of the investigator)\n   3. Total hemoglobin ≥ 9 g\u002FdL unless anemia is due to marrow involvement of CLL (per the discretion of the investigator)\n8. Measured or estimated creatinine clearance ≥ 45 mL\u002Fmin by institutional standard method.\n9. Life expectancy \\> 3 months\n10. For women of childbearing potential (WOCBP): agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \\\u003C 1% per year, and agreement to refrain from donating eggs, during the treatment period and for at least 3 months after the last dose of mosunetuzumab and 3 months after the last dose of tocilizumab (if applicable).\n\n    1. It is recommended to remain abstinent or use contraception for 12 months after the final dose of cyclophosphamide, doxorubicin, or vincristine.\n    2. A woman is considered to be of childbearing potential (WOCBP) if she is postmenarchal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and\u002For uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.\n    3. Examples of contraceptive methods with a failure rate of \\\u003C 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.\n    4. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.\n    5. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the Informed Consent Form.\n11. For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:\n\n    1. With a female partner of childbearing potential or pregnant female partner, men must remain abstinent or use a condom during the treatment period and for 60 days after the final dose of tocilizumab (if applicable) and must remain abstinent or use a condom for 12 months after the final dose of cyclophosphamide, doxorubicin, or vincristine to avoid exposing the embryo. Men must refrain from donating sperm during this same period.\n    2. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure. If required per local guidelines or regulations, information about the reliability of abstinence will be described in the Informed Consent Form.\n\nExclusion Criteria:\n\n1. Pregnant or breastfeeding or intending to become pregnant during the study or within 3 months after the final dose of mosunetuzumab.\n\n   a) WOCBP must have a negative serum pregnancy test result within 14 days prior to initiation of study treatment. If a serum pregnancy test has not been performed within 14 days prior to receiving first study treatment, a negative urine pregnancy test result (performed within 7 days prior to study treatment) must be available.\n2. Participants who have received any of the following treatments prior to study entry:\n\n   a) Treatment with mosunetuzumab or other CD20\u002FCD3-directed bispecific antibodies.\n3. Participants who have received any of the following treatments, whether investigational or approved, given to treat RS, within the respective time periods prior to initiation of study treatment:\n\n   1. Autologous SCT within 100 days prior to first mosunetuzumab administration.\n   2. Allogeneic stem cell transplant for CLL\n   3. CAR T-cell therapy for CLL within 100 days before first study treatment\n   4. Systemic corticosteroid treatment ≤ 20 mg\u002Fday prednisone or equivalent to control symptoms related to disease progression for a maximum of 5 days before starting C1D1 and inhaled corticosteroids are permitted.\n4. Central nervous system (CNS) involvement as documented by spinal fluid cytology or imaging.\n5. Transformation of CLL to prolymphocytic leukemia.\n6. History of prior malignancy, except for conditions as listed below if patients have recovered from the acute side effects incurred as a result of previous therapy:\n\n   1. Malignancies treated with curative intent and with no known active disease present for ≥ 2 years before enrollment.\n   2. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.\n   3. Adequately treated cervical carcinoma in situ without evidence of disease.\n   4. Surgically\u002Fadequately treated low grade, early stage, localized prostate cancer without evidence of disease.\n7. Any of the following laboratory abnormalities:\n\n   1. Calculated creatinine Clearance \\\u003C 45 mL\u002Fmin (by institutional standard method.).\n   2. Absolute neutrophil count (ANC) \\\u003C 1.0 x 109\u002FL, unless secondary to bone marrow involvement by CLL.\n   3. Platelet count \\\u003C75 x 109\u002FL except if thrombocytopenia is clearly due to marrow involvement of CLL (per the discretion of the investigator) for which exclusion criteria would be platelet count \\\u003C 30 x 109\u002FL.\n   4. Serum aspartate aminotransferase (AST)\u002Fserum glutamic-oxaloacetictransaminase (SGOT) or alanine transaminase (ALT)\u002Fserum glutamate pyruvate transaminase (SGPT) \\>2.5 x upper limit of normal (ULN).\n   5. Serum total bilirubin \\> 1.5 x ULN, except in cases of Gilbert's syndrome.\n8. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibody therapy (or recombinant antibody-related fusion proteins)\n9. Contraindication to tocilizumab.\n10. Presence of any autoimmune disorder including autoimmune hemolytic anemia or autoimmune thrombocytopenia active at the moment of first dose of therapy.\n\n    a) Participants with a history of disease-related immune thrombocytopenic purpura or autoimmune hemolytic anemia may be eligible.\n11. History of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Exceptions include the following:\n\n    1. Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.\n    2. Participants with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.\n    3. Participants with a remote history of, or well-controlled autoimmune disease, with a treatment-free interval from immunosuppressive therapy for 12 months may be eligible after review and discussion with the Coordinators.\n12. History of solid organ transplantation\n13. Participants with infections requiring IV treatment with antibiotics or hospitalization (Grade 3 or 4) within the last 4 weeks prior to enrollment or known active bacterial, viral (including SARS-CoV-2), fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment.\n14. History of confirmed progressive multifocal leukoencephalopathy (PML)\n15. Positive serologic HIV test at screening\n16. Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen \\[HBsAg\\] serology). Participants with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HBsAg) may be included if hepatitis B virus (HBV) DNA is undetectable at the time of screening. These participants must be willing to undergo monthly DNA testing and appropriate prophylactic antiviral therapy as indicated.\n17. Acute or chronic hepatitis C virus (HCV) infection. Participants who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation.\n18. Known or suspected chronic active Epstein Barr Virus infection (CAEBV).\n19. Patients with history of macrophage activation syndrome (MAS)\u002Fhemophagocytic lymphohistiocytosis (HLH)\n20. Received a live, attenuated vaccine within 4 weeks before first dose of study treatment, or in whom it is anticipated that such a live attenuated vaccine will be required during the study period or within 5 months after the final dose of study treatment.\n21. Left ventricular ejection fraction (LVEF) \\\u003C50% by multiple-gated acquisition (MUGA) scan or echocardiogram.\n22. Evidence of any significant, concomitant disease that could affect compliance with the protocol or interpretation of results, including, but not limited to:\n\n    1. significant cardiovascular disease (e.g., New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 3 months, unstable arrhythmia, or unstable angina)\n    2. significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm)\n    3. clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis.\n    4. current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease.\n    5. Participants with a history of stroke who have not experienced a stroke or transient ischemic attack in the past year and have no residual neurologic deficits as judged by the investigator are allowed.\n    6. Participants with a history of epilepsy who have had no seizures in the past 2 years with or without anti-epileptic medications can be eligible.\n23. Recent major surgery within 4 weeks prior to first study treatment administration, with the exception of protocol-mandated procedures (e.g., tumor biopsies and bone marrow biopsies)\n24. Participants who are in dependence to the Sponsor or an investigator.\n25. Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes an individual's safe participation in and completion of the study.","79 Years",{"count":202,"type":21},34,[24],"The goal of this clinical trial is to learn if drug Mosunetuzumab works to treat Richter´syndrome . It will also learn about the safety of drug Mosunetuzumab. The main questions it aims to evaluate the efficacy of mosunetuzumab combined with CHOP (M-CHOP) after the end of induction in patients with Richter´s Syndrome who have never received thearapy\n\nWhat medical problems do participants have when taking drug Mosunetuzumab? Patients with Richter´s Syndrome\n\nParticipants will:\n\nTake drug Mosunetuzumab+CHOP during 6 cycle and they if they are not candidate to Alothasplant continuing 11 cycles more with mosunetuzumab on monoterapy Visit the clinic once every 23weeks for checkups and tests",[27],[27],"2025-04-07",{"date":209,"type":32},"2025-04-13",{"date":211,"type":32},"2024-05-15",{"date":213,"type":21},"2028-05-15",{"name":215,"class":39},"GELLC (Grupo Español de Leucemia Linfocítica Crónica)",16,{"id":218,"slug":219,"hasResults":11,"nctId":220,"briefTitle":221,"officialTitle":222,"acronym":4,"eligibilityCriteria":223,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":224,"targetDuration":4,"studyType":226,"phases":4,"briefSummary":227,"conditions":228,"keywords":231,"overallStatus":56,"whyStopped":4,"lastUpdateSubmitDate":233,"lastUpdatePostDateStruct":234,"startDateStruct":236,"completionDateStruct":238,"leadSponsor":240,"locationsCount":4},"100510212","chantreal-world-study-of-duvelisib-in-the-treatment-of-non-hodgkins-lymphoma-nhl-100510212","NCT05923502","(CHANT)Real World Study of Duvelisib in the Treatment of Non-Hodgkin's Lymphoma (NHL)","(CHANT)A Prospective, Multicenter, Non-interventionistic Real-world Study of Duvelisib Capsules in the Treatment of Non-Hodgkin's Lymphoma (NHL).","Inclusion Criteria:\n\n* To participate in the study voluntarily and sign the informed consent (ICF), with good compliance and cooperative visits;\n* Patients must be ≥ 18 years of age (Based on the date of signing the informed Consent (ICF));\n* Pathologically or Histologically confirmed NHL including but not limited to the following subtypes:\n\n  1. Follicular lymphoma (FL);\n  2. Chronic lymphocytic leukemia\u002Fsmall lymphocytic lymphoma or Richter syndrome (CLL\u002FSLL or RS);\n  3. Marginal zone lymphoma (MZL);\n  4. Peripheral T-cell lymphoma (PTCL);\n  5. Diffuse large B-cell lymphoma (DLBCL).\n* Patients who have received at least one systemic chemotherapy and have relapsed at the end of the treatment or progressed during treatment;\n* Must have adequate organ function defined by the following laboratory parameters:\n\n  1. Bone marrow function: Absolute neutrophil count (ANC) ≥ 0.5 × 10\\^9\u002FL, Platelet count (PLT) ≥ 25 × 10\\^9\u002FL, blood transfusion can be used before medication;\n  2. Liver and kidney function: Aspartate transaminase (AST) and alanine aminotransferase (ALT)≤5.0 × ULN;\n  3. Estimated creatinine clearance value ≥30 milliliters\u002Fminute (as determined by the Cockcroft-Gault method).\n* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2;\n* Patients with infections should be treated first and then considered for enrollment when the infection is under control.\n\nExclusion Criteria:\n\n* Female subjects who are pregnant or breastfeeding;\n* Estimated lifetime is less than 3 months;\n* In the investigator's judgment, patients who require but are unable to receive prophylactic treatment for Pneumocystis or herpes simplex virus (HSV) prior to trial drug treatment;\n* History or concurrent condition of interstitial lung disease of any severity and\u002For severely impaired lung function;\n* Prior history of drug-induced colitis or drug-induced interstitial pneumonia;\n* Known hypersensitivity to Duvelisib or its excipients;\n* Administration of medications or foods that are strong inhibitors or inducers of CYP3A beginning 2 weeks prior to the first dose of Duvelisib;\n* According to the judgement of the researcher, there are concomitant diseases that seriously endanger the safety of patients or affect the completion of the study.",{"count":225,"type":21},200,"OBSERVATIONAL","This is a multicenter, non-interventional and prospective real-world study to evaluate the efficacy and safety of Duvelisib capsules in patients with non-Hodgkin's lymphoma.",[109,229,27,111,230,108],"Chronic Lymphocytic Leukemia\u002FSmall Lymphocytic Lymphoma","Peripheral T Cell Lymphoma",[232],"NHL; Duvelisib","2023-10-18",{"date":235,"type":32},"2023-10-23",{"date":237,"type":21},"2023-10-20",{"date":239,"type":21},"2027-11-30",{"name":241,"class":39},"Ruijin Hospital",{"id":243,"slug":244,"hasResults":11,"nctId":245,"briefTitle":246,"officialTitle":247,"acronym":248,"eligibilityCriteria":249,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":250,"targetDuration":4,"studyType":22,"phases":252,"briefSummary":253,"conditions":254,"keywords":255,"overallStatus":28,"whyStopped":4,"lastUpdateSubmitDate":140,"lastUpdatePostDateStruct":261,"startDateStruct":263,"completionDateStruct":265,"leadSponsor":267,"locationsCount":216},"100354777","phase-2-a-trial-of-chop-r-therapy-with-or-without-acalabrutinib-in-patients-with-newly-diagnosed-richters-syndrome-100354777","NCT03899337","A Trial of CHOP-R Therapy, With or Without Acalabrutinib, in Patients With Newly Diagnosed Richter's Syndrome","A Phase II, Randomised Study of CHOP-R in Combination With Acalabrutinib Compared to CHOP-R in Patients With Newly Diagnosed Richter's Syndrome and a Platform for Initial Investigations Into Activity of Novel Treatments in Relapsed\u002FRefractory and Newly Diagnosed Richter's Syndrome.","STELLAR","Entry criteria for randomised trial component (standard of care and experimental arms):\n\nInclusion criteria for the randomised trial component:\n\n* Suitable for anthracycline-containing chemo-immunotherapy.\n* Patients with CLL and newly diagnosed biopsy proven DLBCL-type RS.\n* ECOG performance status of 0, 1, 2 or 3.\n* Age 16 years and over.\n* Signed written informed consent prior to performing any study-specific procedures.\n\nExclusion criteria for the randomised trial component:\n\n* Prior therapy with CHOP or any anthracycline containing treatment at any time prior to randomisation. (Please note that pre-treatment with prednisolone up to 2mg\u002Fkg is allowed for up to 14 days prior to the start of treatment).\n* Ibrutinib-exposed CLL patients who have been newly diagnosed with RS within four weeks of their last dose of ibrutinib. (Ibrutinib-exposed CLL patients who discontinue ibrutinib due to toxicity or progressive CLL and later (more than four weeks) develop RS are not excluded from the randomised trial component).\n* Previous acalabrutinib exposure. (Prior exposure to other Bruton tyrosine kinase (BTK), phosphoinositide-3-kinase (PI3K), or BCL-2 inhibitors is permitted, with the exception of patients who have progressed on ibrutinib - see exclusion criterion above).\n* Known central nervous system (CNS) involvement of CLL or DLBCL.\n* Any other active malignancy that requires active treatment, with the exception of basal cell carcinoma, in-situ cervical cancer, and non-invasive squamous cell carcinoma of the skin.\n* Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, and active hepatitis\n* Positive serology for Hepatitis B (HB) defined as a positive test for HB surface antigen (HBsAg). In addition, if negative for HBsAg but HB core antibody (HBcAb) positive (regardless of HBsAb status), a HBV deoxyribonucleic acid (DNA) test will be performed and if positive the patient will be excluded.\n* Known human immunodeficiency virus (HIV) positive.\n* Patients with active bleeding or history of bleeding diathesis (e.g. haemophilia, von Willebrand disease).\n* Patients receiving therapeutic anticoagulation with warfarin or equivalent (e.g. phenprocoumon).\n* Uncorrected prolonged prothrombin time (PT) or an activated partial thromboplastin time (APTT) \\> 2 x the upper limit of normal (ULN).\n* Major surgery within 30 days prior to randomisation and\u002For inadequate recovery (at Investigators discretion) from any prior major surgery, toxicity or complications.\n* Patients with malabsorption syndrome or medical conditions significantly affecting gastrointestinal function.\n* Clinically significant cardiac disease including unstable angina, uncontrolled congestive heart failure, and unstable arrhythmias requiring therapy, with the exception of extra systoles or minor conduction abnormalities. Stable and controlled atrial fibrillation is not an exclusion.\n* Significant concurrent, uncontrolled severe medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.\n* History of significant cerebrovascular disease in the 6 months prior to randomisation, including intracranial haemorrhage.\n* Known or suspected hypersensitivity to components of the investigational products\n* Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to proposed start of treatment unless discussed and approved by the Chief Investigator or Clinical Coordinator via the Trials Office.\n* Current participation in any other interventional clinical study.\n* Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder).\n* Breast feeding women or women with a positive pregnancy test at screening.\n* Women of childbearing potential and men not willing to use highly effective contraception during study and for 12 months after last dose of study therapy. Highly effective contraception is defined as abstinence, hormonal birth control, intrauterine devices, vasectomy\u002Fsurgical sterilisation.\n\nEntry criteria for single-arm relapsed Cohort 1:\n\nInclusion criteria for Cohort 1 (progressive RS following chemo-immunotherapy):\n\n* Patients with relapsed\u002Frefractory RS who received anthracycline based chemotherapy with anti-CD20 monoclonal antibody If fewer than the expected number of patients from the randomised component enter into Cohort 1, patients from outside STELLAR with relapsed\u002Frefractory RS following chemo-immunotherapy (anthracycline based chemotherapy with anti-CD20 monoclonal antibody) will be able to join this cohort if they meet the eligibility criteria. The Trials Office will alert sites by email if any slots are released for patients outside of STELLAR, these must be booked with the Trials Office prior to registration.\n* ECOG performance status of 0, 1, 2 or 3.\n* Age 16 years and over.\n* Signed written informed consent prior to performing any study-specific procedures.\n\nExclusion criteria for Cohort 1 (progressive RS following chemo-immunotherapy):\n\n* Previous acalabrutinib exposure. (Prior exposure to other Bruton tyrosine kinase (BTK), phosphoinositide-3-kinase (PI3K), or BCL-2 inhibitors is permitted).\n* Known central nervous system (CNS) involvement of CLL or DLBCL.\n* Any other active malignancy that requires active treatment, with the exception of basal cell carcinoma, in-situ cervical cancer, and non-invasive squamous cell carcinoma of the skin.\n* Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, and active hepatitis\n* Positive serology for Hepatitis B (HB) defined as a positive test for HB surface antigen (HBsAg). In addition, if negative for HBsAg but HB core antibody (HBcAb) positive (regardless of HBsAb status), a HBV deoxyribonucleic acid (DNA) test will be performed and if positive the patient will be excluded.\n* Known human immunodeficiency virus (HIV) positive.\n* Patients with active bleeding or history of bleeding diathesis (e.g. haemophilia, von Willebrand disease).\n* Patients receiving therapeutic anticoagulation with warfarin or equivalent (e.g. phenprocoumon).\n* Uncorrected prolonged prothrombin time (PT) or an activated partial thromboplastin time (APTT) \\> 2 x the upper limit of normal (ULN).\n* Major surgery within 30 days prior to registration and\u002For inadequate recovery (at Investigators discretion) from any prior major surgery, toxicity or complications.\n* Patients with malabsorption syndrome or medical conditions significantly affecting gastrointestinal function.\n* Clinically significant cardiac disease including unstable angina, uncontrolled congestive heart failure, and unstable arrhythmias requiring therapy, with the exception of extra systoles or minor conduction abnormalities. Stable and controlled atrial fibrillation is not an exclusion.\n* Significant concurrent, uncontrolled severe medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.\n* History of significant cerebrovascular disease in the 6 months prior to registration, including intracranial haemorrhage.\n* Known or suspected hypersensitivity to components of the investigational products\n* Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to proposed start of treatment unless discussed and approved by the Chief Investigator or Clinical Coordinator via the Trials Office.\n* Current participation in any other interventional clinical study.\n* Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder).\n* Breast feeding women or women with a positive pregnancy test at screening.\n* Women of childbearing potential and men not willing to use highly effective contraception during study and for 12 months after last dose of study therapy. Highly effective contraception is defined as abstinence, hormonal birth control, intrauterine devices, vasectomy\u002Fsurgical sterilisation.\n\nEntry criteria for single arm Cohort 2\n\nInclusion criteria for Cohort 2 (anthracycline-naïve RS patients, diagnosed while on ibrutinib):\n\n* Ibrutinib-exposed CLL patients who have developed biopsy-proven DLBCL-type RS within four weeks of last dose of ibrutinib.\n* No previous anthracycline treatment and suitable for anthracycline-containing chemo-immunotherapy.\n* Patients with CLL and newly diagnosed biopsy proven DLBCL-type RS.\n* ECOG performance status of 0, 1, 2 or 3.\n* Age 16 years and over.\n* Signed written informed consent prior to performing any study-specific procedures.\n\nExclusion criteria for Cohort 2 (anthracycline-naïve RS patients, diagnosed while on ibrutinib):\n\n* Prior therapy with CHOP or any anthracycline containing treatment at any time prior to registration. (Please note that pre-treatment with prednisolone up to 2mg\u002Fkg is allowed for up to 14 days prior to the start of treatment).\n* Previous acalabrutinib exposure. (Prior exposure to other Bruton tyrosine kinase (BTK), phosphoinositide-3-kinase (PI3K), or BCL-2 inhibitors is permitted)\n* Known central nervous system (CNS) involvement of CLL or DLBCL.\n* Any other active malignancy that requires active treatment, with the exception of basal cell carcinoma, in-situ cervical cancer, and non-invasive squamous cell carcinoma of the skin.\n* Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, and active hepatitis\n* Positive serology for Hepatitis B (HB) defined as a positive test for HB surface antigen (HBsAg). In addition, if negative for HBsAg but HB core antibody (HBcAb) positive (regardless of HBsAb status), a HBV deoxyribonucleic acid (DNA) test will be performed and if positive the patient will be excluded.\n* Known human immunodeficiency virus (HIV) positive.\n* Patients with active bleeding or history of bleeding diathesis (e.g. haemophilia, von Willebrand disease).\n* Patients receiving therapeutic anticoagulation with warfarin or equivalent (e.g. phenprocoumon).\n* Uncorrected prolonged prothrombin time (PT) or an activated partial thromboplastin time (APTT) \\> 2 x the upper limit of normal (ULN).\n* Major surgery within 30 days prior to registration and\u002For inadequate recovery (at Investigators discretion) from any prior major surgery, toxicity or complications.\n* Patients with malabsorption syndrome or medical conditions significantly affecting gastrointestinal function.\n* Clinically significant cardiac disease including unstable angina, uncontrolled congestive heart failure, and unstable arrhythmias requiring therapy, with the exception of extra systoles or minor conduction abnormalities. Stable and controlled atrial fibrillation is not an exclusion.\n* Significant concurrent, uncontrolled severe medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.\n* History of significant cerebrovascular disease in the 6 months prior to registration, including intracranial haemorrhage.\n* Known or suspected hypersensitivity to components of the investigational products\n* Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to proposed start of treatment unless discussed and approved by the Chief Investigator or Clinical Coordinator via the Trials Office.\n* Current participation in any other interventional clinical study.\n* Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder).\n* Breast feeding women or women with a positive pregnancy test at screening.\n* Women of childbearing potential and men not willing to use highly effective contraception during study and for 12 months after last dose of study therapy. Highly effective contraception is defined as abstinence, hormonal birth control, intrauterine devices, vasectomy\u002Fsurgical sterilisation.",{"count":251,"type":21},105,[24],"The STELLAR trial will assess the effect of acalabrutinib taken in combination with CHOP-R compared to taking CHOP-R alone in patients with newly diagnosed Richter's Syndrome (RS). It will also be a platform to test other new drugs that show potential for treating RS. Chronic lymphocytic Leukaemia (CLL) is the most common blood cancer in adults, usually in their 70s or older. In a few patients, CLL can transform from a slow-growing cancer into an aggressive lymphoma called Richter's Syndrome. RS is very difficult to treat and patients have a short life-expectancy - usually a few months after diagnosis. Treatment for Richter's Syndrome in the UK is CHOP (four chemotherapy drugs) plus rituximab ('R' - an antibody treatment). The CHOP-R treatment is given as a standard of care for RS but has limited benefit - it is often temporary to extend life. Richter's Syndrome returns in most patients who then die from this disease. The STELLAR trial will investigate if a new drug called acalabrutinib, which is effective used by itself in patients with relapsed CLL and also some with Richter's Syndrome, will improve outcomes for newly diagnosed patients with RS. Acalabrutinib blocks a protein in CLL which can stop the cancer growing.\n\nParticipants who have Richter's Syndrome and are suitable for CHOP-R will be recruited by specialised hospitals across the UK. People with another cancer, heart problems, or recent stroke cannot take part. Participants will have a lymph node biopsy, 3-4 bone marrow biopsies, blood samples, and PET-CT and CT scans. CHOP-R is given in a hospital every three weeks up to 6 times. All participants will receive CHOP-R; half will also receive acalabrutinib. When treatment with CHOP-R ends the patients who had acalabrutinib can continue to take it; patients who had CHOP-R alone may have acalabrutinib if their Richter's Syndrome returns after CHOP-R.",[27],[256,160,257,258,259,108,260],"Chronic Lymphocytic Leukaemia","Richter's Syndrome","CHOP-R","Acalabrutinib","non-Hodgkin Lymphoma",{"date":262,"type":32},"2023-01-09",{"date":264,"type":32},"2019-07-23",{"date":266,"type":21},"2027-05-31",{"name":268,"class":39},"University of Birmingham"]