Diffuse Large B Cell Lymphoma (DLBCL)Phase 1NCT07638982
Axatilimab + CAR-T for High-Risk Lymphoma
A Phase 1 study testing Axatilimab in people with Diffuse Large B Cell Lymphoma (DLBCL) and Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma, run by Northside Hospital, Inc. at 1 site in United States.
Trial summary
Axatilimab + CAR-T in High-Risk Lymphoma Read more about this study
- Who is it for?
- Ages 8 years and older
- Conditions the study is for
- 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)
- What is being tested?
- Axatilimab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Dec 2026to 31 Dec 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- Allogeneic transplant within 100 days of enrollment
- Active acute or chronic graft versus host disease
- History of acute or chronic pancreatitis
- History of myositis
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Northside Hospital
Atlanta, Georgia, 30342
Caitlin Guzowski, MBA, MHA, CCRC, 404-851-8523, caitlin.guzowski@northside.com
About this study
Official title: An Open-label, Phase I Trial, With an Expansion Cohort: Macrophage Conditioning to Synergize With CAR-T in High-risk Lymphoma (MAC-SHIFT)
Axatilimab + CAR-T in High-Risk Lymphoma
- Conditions
- 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
- Being tested
- Axatilimab
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Pyloric Stenosis, Hypertrophic, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AxatilimabDrug
Dose Level -1: 0.1mg/kg Dose Level +1: 0.3mg/kg Dose Level +2: 1mg/kg Dose Level +3: 3mg/kg
| Study group | Role | What they receive |
|---|---|---|
| Axatilimab + Commercial CAR T cell therapy | Experimental | Not described Receives: Drug: Axatilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 year
Estimate 1 year progression-free survival
Estimate 1 year progression-free survival by assessing disease status at 1 year following CAR T infusion
Measured: 1 year
Secondary outcomes (5)
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
Measured: 1 year
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
Measured: 1 year
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
Measured: 1 year
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
Measured: 1 year
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 grade 3 and 4 adverse events using the CTCAE version 6 criteria
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2026
- Study start31 Dec 2026 (estimated)
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B Cell Lymphoma (DLBCL)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northside Hospital, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07638982
- Sponsor's protocol ID
- NSH 1445
- Status last verified
- Oct 2026
- First submitted
- 5 Jun 2026
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 40381116Kitko 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. doi: 10.1200/JCO.22.00958. Epub 2022 Dec 2.
PubMed 36459673Yan 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.
PubMed 31444250Carniti 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.
PubMed 38359407Jain 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/blood.2020007445.
PubMed 33512407Wang 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.
PubMed 28036275Marchesi 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. doi: 10.1002/hon.2142. Epub 2014 Apr 8. No abstract available.
PubMed 24711044Li 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.
PubMed 31694577Cencini 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.
PubMed 32923089Wang 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/jcm10081768.
PubMed 33921711Shen 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/srep30347.
PubMed 27464733Benner 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/s40425-019-0622-0.
PubMed 31138333Ugel 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/JCI80006. Epub 2015 Sep 1.
PubMed 26325033Noy R, Pollard JW. Tumor-associated macrophages: from mechanisms to therapy. Immunity. 2014 Jul 17;41(1):49-61. doi: 10.1016/j.immuni.2014.06.010.
PubMed 25035953Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008 Jul 24;454(7203):436-44. doi: 10.1038/nature07205.
PubMed 18650914