Axatilimab + CAR-T for High-Risk Lymphoma

Официальное название

An Open-label, Phase I Trial, With an Expansion Cohort: Macrophage Conditioning to Synergize With CAR-T in High-risk Lymphoma (MAC-SHIFT)

Обзор

Axatilimab + CAR-T in High-Risk Lymphoma

Вмешательства

• Препарат Axatilimab
  Dose Level -1: 0.1mg/kg Dose Level +1: 0.3mg/kg Dose Level +2: 1mg/kg Dose Level +3: 3mg/kg

Первичные конечные точки

• Determine the recommended Phase 2 dose (RP2D) of axatilimab [Срок оценки: 1 year]
• Estimate 1 year progression-free survival [Срок оценки: 1 year]

Вторичные конечные точки (5)

• Estimate overall response rate [Срок оценки: 1 year]
• Estimate the overall survival of patients [Срок оценки: 1 year]
• Evaluate duration of response [Срок оценки: 1 year]
• Characterize the safety of axatilimab in combination with CAR T therapy [Срок оценки: 1 year]
• Characterize the safety of axatilimab in combination with CAR T therapy [Срок оценки: 1 year]

Критерии участия

Критерии включения

• 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/AST < 5x ULN
• Bilirubin < 3 x ULN
• Calculated or measured creatinine Clearance ≥ 30 mL/min

Критерии исключения

• KPS <60
• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Northside Hospital — Atlanta

Публикации

• 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/s40261-025-01438-7. Epub 2025 May 17. PMID 40381116
• 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/II Study. J Clin Oncol. 2023 Apr 1;41(10):1864-1875. d PMID 36459673
• 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: 10.1158/1078-0432.CCR-19-0101. Epub 2019 Aug 23. PMID 31444250
• 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/bloodadvances.2024012563. PMID 38359407
• 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) PMID 33512407
• 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/oncotarget.14289. PMID 28036275
• 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+/CD163+ 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. d PMID 24711044
• 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/s12885-019-6208-x. PMID 31694577

Идентификаторы

NCT: NCT07638982 · NSH 1445

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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