[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT07638982":3,"trial-entities:NCT07638982":187,"trial-summary:NCT07638982":195},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":17,"conditions":18,"keywords":25,"study_type":26,"primary_purpose":27,"phases":28,"enrollment_info":30,"interventions":33,"primary_outcomes":40,"secondary_outcomes":48,"sex":63,"minimum_age":64,"maximum_age":17,"healthy_volunteers":65,"eligibility_criteria":66,"std_ages":91,"locations":95,"central_contacts":111,"overall_officials":117,"references":118,"see_also_links":186},"NCT07638982","NSH 1445","Axatilimab + CAR-T for High-Risk Lymphoma","An Open-label, Phase I Trial, With an Expansion Cohort: Macrophage Conditioning to Synergize With CAR-T in High-risk Lymphoma (MAC-SHIFT)","NOT_YET_RECRUITING","2029-12-31","2026-06","2026-06-10","2026-10-31","Northside Hospital, Inc.","OTHER",true,"Axatilimab + CAR-T in High-Risk Lymphoma",null,[19,20,21,22,23,24],"Diffuse Large B Cell Lymphoma (DLBCL)","Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma","High-grade B-cell Lymphoma (HGBCL)","High-Grade B-Cell Lymphoma, Nos","PMBCL","Follicular Grade 3 Lymphoma",[],"INTERVENTIONAL","TREATMENT",[29],"PHASE1",{"count":31,"type":32},29,"ESTIMATED",[34],{"type":35,"name":36,"description":37,"armGroupLabels":38},"DRUG","Axatilimab","Dose Level -1: 0.1mg\u002Fkg Dose Level +1: 0.3mg\u002Fkg Dose Level +2: 1mg\u002Fkg Dose Level +3: 3mg\u002Fkg",[39],"Axatilimab + Commercial CAR T cell therapy",[41,45],{"measure":42,"description":43,"timeFrame":44},"Determine the recommended Phase 2 dose (RP2D) of axatilimab","Determine the recommended Phase 2 dose (RP2D) of axatilimab in combination with CAR T cell therapy by following a fast-track dose escalation design and assessing adverse events, using the CTCAE Version 6, related to axatilimab","1 year",{"measure":46,"description":47,"timeFrame":44},"Estimate 1 year progression-free survival","Estimate 1 year progression-free survival by assessing disease status at 1 year following CAR T infusion",[49,52,55,58,61],{"measure":50,"description":51,"timeFrame":44},"Estimate overall response rate","Estimate overall response rate (a combination of complete and partial responders) by assessing disease status at 1 year following CAR T infusion",{"measure":53,"description":54,"timeFrame":44},"Estimate the overall survival of patients","Estimate the overall survival of patients by following survival status and cause of death for 1 year after CAR T infusion",{"measure":56,"description":57,"timeFrame":44},"Evaluate duration of response","Evaluate duration of response by assessing disease status at multiple timepoints (Days +30, 100, 180, and 365) within 1 year after CAR T infusion",{"measure":59,"description":60,"timeFrame":44},"Characterize the safety of axatilimab in combination with CAR T therapy","Characterize the safety of axatilimab in combination with CAR T therapy by assessing the incidence of cytokine release syndrome and immune-effector cell associated neurotoxcity syndrome according to ASTCT consensus criteria",{"measure":59,"description":62,"timeFrame":44},"Characterize the safety of axatilimab in combination with CAR T therapy by assessing the incidence of grade 3 and 4 adverse events using the CTCAE version 6 criteria","ALL","8 Years",false,{"inclusion":67,"exclusion":79,"raw_text":90},[68,69,70,71,72,73,74,75,76,77,78],"Age ≥ 18 years","Histologically confirmed large B-cell lymphoma","Presence of one or more high-risk features","Eligible to receive CAR-T according to the FDA label","Measurable disease by CT or PET","Adequate organ function unless related to lymphoma involvement:","Pulse oximetry ≥ 92% on room air","Ejection Fraction ≥ 40%","ALT\u002FAST \\\u003C 5x ULN","Bilirubin \\\u003C 3 x ULN","Calculated or measured creatinine Clearance ≥ 30 mL\u002Fmin",[80,81,82,83,84,85,86,87,88,89],"KPS \\\u003C60","Second malignancy with a high metastatic potential within 3 years","Active CNS involvement. Treated CNS disease is allowed","Active HBV or HCV infection.","Active uncontrolled infections","Known HIV positive status","Allogeneic transplant within 100 days of enrollment","Active acute or chronic graft versus host disease","History of acute or chronic pancreatitis","History of myositis","Inclusion Criteria:\n\n* Age ≥ 18 years\n* Histologically confirmed large B-cell lymphoma\n* Presence of one or more high-risk features\n* Eligible to receive CAR-T according to the FDA label\n* Measurable disease by CT or PET\n* Adequate organ function unless related to lymphoma involvement:\n* Pulse oximetry ≥ 92% on room air\n* Ejection Fraction ≥ 40%\n* ALT\u002FAST \\\u003C 5x ULN\n* Bilirubin \\\u003C 3 x ULN\n* Calculated or measured creatinine Clearance ≥ 30 mL\u002Fmin\n\nExclusion Criteria:\n\n* KPS \\\u003C60\n* Second malignancy with a high metastatic potential within 3 years\n* Active CNS involvement. Treated CNS disease is allowed\n* Active HBV or HCV infection.\n* Active uncontrolled infections\n* Known HIV positive status\n* Allogeneic transplant within 100 days of enrollment\n* Active acute or chronic graft versus host disease\n* History of acute or chronic pancreatitis\n* History of myositis",[92,93,94],"CHILD","ADULT","OLDER_ADULT",[96],{"facility":97,"city":98,"state":99,"zip":100,"country":101,"contacts":102,"geoPoint":108},"Northside Hospital","Atlanta","Georgia","30342","United States",[103],{"name":104,"role":105,"phone":106,"email":107},"Caitlin Guzowski, MBA, MHA, CCRC","CONTACT","404-851-8523","caitlin.guzowski@northside.com",{"lat":109,"lon":110},33.749,-84.38798,[112,116],{"name":113,"role":105,"phone":114,"email":115},"Joseph Maakaron, MD","404-255-1930","jmaakaron@bmtga.com",{"name":104,"role":105,"phone":106,"email":107},[],[119,123,126,129,132,135,138,141,144,147,150,153,156,159,162,165,168,171,174,177,180,183],{"pmid":120,"type":121,"citation":122},"40381116","BACKGROUND","Haranaka M, Kinami K, Yang YO, Li H, Pratta M, Suzukawa K. Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Axatilimab in Healthy Japanese Male Participants: Results from a Phase 1, Randomized, Double-Blind, Dose-Escalation Study. Clin Drug Investig. 2025 Jun;45(6):327-334. doi: 10.1007\u002Fs40261-025-01438-7. Epub 2025 May 17.",{"pmid":124,"type":121,"citation":125},"36459673","Kitko CL, Arora M, DeFilipp Z, Zaid MA, Di Stasi A, Radojcic V, Betts CB, Coussens LM, Meyers ML, Qamoos H, Ordentlich P, Kumar V, Quaranto C, Schmitt A, Gu Y, Blazar BR, Wang TP, Salhotra A, Pusic I, Jagasia M, Lee SJ. Axatilimab for Chronic Graft-Versus-Host Disease After Failure of at Least Two Prior Systemic Therapies: Results of a Phase I\u002FII Study. J Clin Oncol. 2023 Apr 1;41(10):1864-1875. doi: 10.1200\u002FJCO.22.00958. Epub 2022 Dec 2.",{"pmid":127,"type":121,"citation":128},"31444250","Yan ZX, Li L, Wang W, OuYang BS, Cheng S, Wang L, Wu W, Xu PP, Muftuoglu M, Hao M, Yang S, Zhang MC, Zheng Z, Li J, Zhao WL. Clinical Efficacy and Tumor Microenvironment Influence in a Dose-Escalation Study of Anti-CD19 Chimeric Antigen Receptor T Cells in Refractory B-Cell Non-Hodgkin's Lymphoma. Clin Cancer Res. 2019 Dec 1;25(23):6995-7003. doi: 10.1158\u002F1078-0432.CCR-19-0101. Epub 2019 Aug 23.",{"pmid":130,"type":121,"citation":131},"38359407","Carniti C, Caldarelli NM, Agnelli L, Torelli T, Ljevar S, Jonnalagadda S, Zanirato G, Fardella E, Stella F, Lorenzini D, Brich S, Arienti F, Dodero A, Chiappella A, Magni M, Corradini P. Monocytes in leukapheresis products affect the outcome of CD19-targeted CAR T-cell therapy in patients with lymphoma. Blood Adv. 2024 Apr 23;8(8):1968-1980. doi: 10.1182\u002Fbloodadvances.2024012563.",{"pmid":133,"type":121,"citation":134},"33512407","Jain MD, Zhao H, Wang X, Atkins R, Menges M, Reid K, Spitler K, Faramand R, Bachmeier C, Dean EA, Cao B, Chavez JC, Shah B, Lazaryan A, Nishihori T, Hussaini M, Gonzalez RJ, Mullinax JE, Rodriguez PC, Conejo-Garcia JR, Anasetti C, Davila ML, Locke FL. Tumor interferon signaling and suppressive myeloid cells are associated with CAR T-cell failure in large B-cell lymphoma. Blood. 2021 May 13;137(19):2621-2633. doi: 10.1182\u002Fblood.2020007445.",{"pmid":136,"type":121,"citation":137},"28036275","Wang J, Gao K, Lei W, Dong L, Xuan Q, Feng M, Wang J, Ye X, Jin T, Zhang Z, Zhang Q. Lymphocyte-to-monocyte ratio is associated with prognosis of diffuse large B-cell lymphoma: correlation with CD163 positive M2 type tumor-associated macrophages, not PD-1 positive tumor-infiltrating lymphocytes. Oncotarget. 2017 Jan 17;8(3):5414-5425. doi: 10.18632\u002Foncotarget.14289.",{"pmid":139,"type":121,"citation":140},"24711044","Marchesi F, Cirillo M, Bianchi A, Gately M, Olimpieri OM, Cerchiara E, Renzi D, Micera A, Balzamino BO, Bonini S, Onetti Muda A, Avvisati G. High density of CD68+\u002FCD163+ tumour-associated macrophages (M2-TAM) at diagnosis is significantly correlated to unfavorable prognostic factors and to poor clinical outcomes in patients with diffuse large B-cell lymphoma. Hematol Oncol. 2015 Jun;33(2):110-2. doi: 10.1002\u002Fhon.2142. Epub 2014 Apr 8. No abstract available.",{"pmid":142,"type":121,"citation":143},"31694577","Li YL, Shi ZH, Wang X, Gu KS, Zhai ZM. Tumor-associated macrophages predict prognosis in diffuse large B-cell lymphoma and correlation with peripheral absolute monocyte count. BMC Cancer. 2019 Nov 6;19(1):1049. doi: 10.1186\u002Fs12885-019-6208-x.",{"pmid":145,"type":121,"citation":146},"32923089","Cencini E, Fabbri A, Schiattone L, Sicuranza A, Mecacci B, Granai M, Mancini V, Lazzi S, Bocchia M, Leoncini L. Prognostic impact of tumor-associated macrophages, lymphocyte-to-monocyte and neutrophil-to-lymphocyte ratio in diffuse large B-cell lymphoma. Am J Blood Res. 2020 Aug 25;10(4):97-108. eCollection 2020.",{"pmid":148,"type":121,"citation":149},"33921711","Wang Z, Jiang R, Li Q, Wang H, Tao Q, Zhai Z. Elevated M-MDSCs in Circulation Are Indicative of Poor Prognosis in Diffuse Large B-Cell Lymphoma Patients. J Clin Med. 2021 Apr 19;10(8):1768. doi: 10.3390\u002Fjcm10081768.",{"pmid":151,"type":121,"citation":152},"27464733","Shen L, Li H, Shi Y, Wang D, Gong J, Xun J, Zhou S, Xiang R, Tan X. M2 tumour-associated macrophages contribute to tumour progression via legumain remodelling the extracellular matrix in diffuse large B cell lymphoma. Sci Rep. 2016 Jul 28;6:30347. doi: 10.1038\u002Fsrep30347.",{"pmid":154,"type":121,"citation":155},"31138333","Benner B, Scarberry L, Suarez-Kelly LP, Duggan MC, Campbell AR, Smith E, Lapurga G, Jiang K, Butchar JP, Tridandapani S, Howard JH, Baiocchi RA, Mace TA, Carson WE 3rd. Generation of monocyte-derived tumor-associated macrophages using tumor-conditioned media provides a novel method to study tumor-associated macrophages in vitro. J Immunother Cancer. 2019 May 28;7(1):140. doi: 10.1186\u002Fs40425-019-0622-0.",{"pmid":157,"type":121,"citation":158},"26325033","Ugel S, De Sanctis F, Mandruzzato S, Bronte V. Tumor-induced myeloid deviation: when myeloid-derived suppressor cells meet tumor-associated macrophages. J Clin Invest. 2015 Sep;125(9):3365-76. doi: 10.1172\u002FJCI80006. Epub 2015 Sep 1.",{"pmid":160,"type":121,"citation":161},"25035953","Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity. 2014 Jul 17;41(1):49-61. doi: 10.1016\u002Fj.immuni.2014.06.010.",{"pmid":163,"type":121,"citation":164},"18650914","Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008 Jul 24;454(7203):436-44. doi: 10.1038\u002Fnature07205.",{"pmid":166,"type":121,"citation":167},"37874957","Iacoboni G, Navarro V, Martin-Lopez AA, Rejeski K, Kwon M, Jalowiec KA, Amat P, Reguera-Ortega JL, Gallur L, Blumenberg V, Gutierrez-Herrero S, Roddie C, Benzaquen A, Delgado-Serrano J, Sanchez-Salinas MA, Bailen R, Carpio C, Lopez-Corral L, Hernani R, Bastos M, O'Reilly M, Martin-Martin L, Subklewe M, Barba P. Recent Bendamustine Treatment Before Apheresis Has a Negative Impact on Outcomes in Patients With Large B-Cell Lymphoma Receiving Chimeric Antigen Receptor T-Cell Therapy. J Clin Oncol. 2024 Jan 10;42(2):205-217. doi: 10.1200\u002FJCO.23.01097. Epub 2023 Oct 24.",{"pmid":169,"type":121,"citation":170},"33180899","Vercellino L, Di Blasi R, Kanoun S, Tessoulin B, Rossi C, D'Aveni-Piney M, Oberic L, Bodet-Milin C, Bories P, Olivier P, Lafon I, Berriolo-Riedinger A, Galli E, Bernard S, Rubio MT, Bossard C, Meignin V, Merlet P, Feugier P, Le Gouill S, Ysebaert L, Casasnovas O, Meignan M, Chevret S, Thieblemont C. Predictive factors of early progression after CAR T-cell therapy in relapsed\u002Frefractory diffuse large B-cell lymphoma. Blood Adv. 2020 Nov 24;4(22):5607-5615. doi: 10.1182\u002Fbloodadvances.2020003001.",{"pmid":172,"type":121,"citation":173},"30837712","Shah NN, Fry TJ. Mechanisms of resistance to CAR T cell therapy. Nat Rev Clin Oncol. 2019 Jun;16(6):372-385. doi: 10.1038\u002Fs41571-019-0184-6.",{"pmid":175,"type":121,"citation":176},"39716447","Galli E, Guarneri A, Sora F, Viscovo M, Pansini I, Maiolo E, Alma E, Annunziata S, Sica S, Leccisotti L, Hohaus S. Baseline Tumor Burden Assessed With AI-Guided PET\u002FCT Total Metabolic Tumor Volume (TMTV) and LDH Levels Predict Efficacy of CAR-T in Aggressive B-Cell Lymphoma. Hematol Oncol. 2025 Jan;43(1):e70029. doi: 10.1002\u002Fhon.70029.",{"pmid":178,"type":121,"citation":179},"32702097","Dean EA, Mhaskar RS, Lu H, Mousa MS, Krivenko GS, Lazaryan A, Bachmeier CA, Chavez JC, Nishihori T, Davila ML, Khimani F, Liu HD, Pinilla-Ibarz J, Shah BD, Jain MD, Balagurunathan Y, Locke FL. High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma. Blood Adv. 2020 Jul 28;4(14):3268-3276. doi: 10.1182\u002Fbloodadvances.2020001900.",{"pmid":181,"type":121,"citation":182},"36964939","Beyar Katz O, Perry C, Grisariu-Greenzaid S, Yehudai-Ofir D, Luttwak E, Avni B, Zuckerman T, Sdayoor I, Stepensky P, Ringelstein-Harlev S, Bar-On Y, Libster D, Sharvit L, Amit O, Greenbaum U, Gold R, Herishanu Y, Benyamini N, Avivi I, Ram R. Response rates of extra-nodal diffuse large B cell lymphoma to anti-CD19-CAR T cells: A real word retrospective multicenter study. Eur J Haematol. 2023 Jul;111(1):63-71. doi: 10.1111\u002Fejh.13968. Epub 2023 Apr 10.",{"pmid":184,"type":121,"citation":185},"30592986","Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016\u002Fj.bbmt.2018.12.758. Epub 2018 Dec 25.",[],{"nct_id":4,"conditions":188,"biomarkers":194},[189,190,191,192,193,20],"Diffuse Large B-Cell Lymphoma","Follicular Lymphoma","High Grade B-Cell Lymphoma","High Grade B-Cell Lymphoma, Not Otherwise Specified","Primary Mediastinal Large B-Cell Lymphoma",[],{"nct_id":4,"found":65,"summary":17,"prompt_version":17}]