Acute Myeloid LeukemiaPhase 1NCT07511062
Axatilimab Combined With Decitabine/Venetoclax for the Treatment of TP53-mutated AML
A Phase 1 study testing Decitabine, Venetoclax and Axatilimab in people with Acute Myeloid Leukemia and TP53 Gene Mutation, run by Northside Hospital, Inc. at 1 site in United States.
Trial summary
Axatilimab combined with Decitabine/Venetoclax for the treatment of TP53-mutated/deleted AML patients Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, TP53 Gene Mutation
- What is being tested?
- Decitabine, Venetoclax and Axatilimab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Jan 2027to 1 Aug 2030
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- MDS/AML or AML with a TP53 mutation or deletion, defined as:
- greater than or equal to 10% AND (one of the following):
- presence of a TP53 mutation
- presence of a TP53 deletion by FISH
- positive TP53 staining on IHC of diagnostic bone marrow
- Either untreated or first salvage (primary refractory or first relapse)
Who cannot join
- KPS <60
- active uncontrolled infection
- history of HIV or active HBV or HBC infection
- currently active second malignancy
- calculated CrCl <40mL/min
- AST and/or ALT and/or direct bilirubin >3x ULN
Show all 11Show fewer
- cardiac ejection fraction <40% or history of uncontrolled cardiac arrhythmias
- history of acute or chronic pancreatitis, history of myositis
- known leukemia involvement of CNS
- hematopoietic stem cell transplantation within 3 months of treatment start and/or persistent non-hematologic toxicities of Grade 2+ related to the transplant
- active acute or chronic GVHD requiring immunosuppressive treatment
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, Inc.
Atlanta, Georgia, 30342
Caitlin Guzowski, 404-851-8523, caitlin.guzowski@northside.com
About this study
Official title: Axatilimab Combined With Decitabine/Venetoclax for the Treatment of TP53-mutated/Deleted AML Patients
Axatilimab combined with Decitabine/Venetoclax for the treatment of TP53-mutated/deleted AML patients
- Conditions
- Acute Myeloid Leukemia, TP53 Gene Mutation
- Being tested
- Decitabine, Venetoclax, Axatilimab
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
20mg/m2/d x5 days (induction \& consolidation)
VenetoclaxDrug
400mg/d x14 days (induction); 400mg/d x7 days (consolidation)
AxatilimabDrug
Dose escalation, given on Days 1 and 15 of each cycle
| Study group | Role | What they receive |
|---|---|---|
| Axatilimab+Decitabine+Venetoclax | Experimental | Not described Receives: Drug: Decitabine; Drug: Venetoclax; Drug: Axatilimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 2 Dose Level determination
To find the recommended phase 2 dose (RP2D) of axatilimab when combined with decitabine and venetoclax by recording adverse events based on the CTCAE v.5.
Measured: 1 year
Estimation of MRD-negative complete remission
To estimate the MRD-negative complete remission rate after 1-2 cycles of induction chemotherapy with decitabine and venetoclax by conducing bone marrow biopsies and disease response assessments after induction
Measured: 2 months
Secondary outcomes (4)
Estimation of Response Rates, Overall Survival
To estimate the complete response rate by evaluating bone marrow biopsies that occur after induction and every 3 months during consolidation
Measured: 1 year
Evaluation of Safety of the Regimen
To evaluate the safety and tolerability of axatilimab when combined with decitabine and venetoclax by recording all adverse events according to the CTCAE v5.0
Measured: 1 year
Estimation of Progression Free Survival
To estimate the progression free survival rate by evaluating bone marrow biopsies that occur after induction and every 3 months during consolidation
Measured: 1 year
Estimation of Overall Survival
To estimate the overall survival rates by contacting patients 1 year after completion of therapy for survival data
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 posted6 Apr 2026
- Study start31 Jan 2027 (estimated)
- Primary completion1 Aug 2029 (estimated)
- Study completion1 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (34)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid LeukemiaStudies 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
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Northside Hospital, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Corporation
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07511062
- Sponsor's protocol ID
- NSH 1436
- Status last verified
- Oct 2026
- First submitted
- 25 Mar 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: Endpoints are looking at overall responses and efficacy
Publications
Wolff D, Cutler C, Lee SJ, Pusic I, Bittencourt H, White J, Hamadani M, Arai S, Salhotra A, Perez-Simon JA, Alousi A, Choe H, Kwon M, Bermudez A, Kim I, Socie G, Chhabra S, Radojcic V, O'Toole T, Tian C, Ordentlich P, DeFilipp Z, Kitko CL; AGAVE-201 Investigators. Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2024 Sep 19;391(11):1002-1014. doi: 10.1056/NEJMoa2401537.
PubMed 39292927Kitko 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 36459673Alexander KA, Flynn R, Lineburg KE, Kuns RD, Teal BE, Olver SD, Lor M, Raffelt NC, Koyama M, Leveque L, Le Texier L, Melino M, Markey KA, Varelias A, Engwerda C, Serody JS, Janela B, Ginhoux F, Clouston AD, Blazar BR, Hill GR, MacDonald KP. CSF-1-dependant donor-derived macrophages mediate chronic graft-versus-host disease. J Clin Invest. 2014 Oct;124(10):4266-80. doi: 10.1172/JCI75935. Epub 2014 Aug 26.
PubMed 25157821Lemmon MA, Schlessinger J. Cell signaling by receptor tyrosine kinases. Cell. 2010 Jun 25;141(7):1117-34. doi: 10.1016/j.cell.2010.06.011.
PubMed 20602996Rosnet O, Birnbaum D. Hematopoietic receptors of class III receptor-type tyrosine kinases. Crit Rev Oncog. 1993;4(6):595-613.
PubMed 7506935Xu L, Xie X, Li X, Duan W, Qiu L, Liu H, Luo Y. Inflammatory level under different p53 mutation status and the regulation role of curcumin in tumor microenvironment. Immunobiology. 2022 Mar;227(2):152177. doi: 10.1016/j.imbio.2022.152177. Epub 2022 Jan 7.
PubMed 35030341Blagih J, Zani F, Chakravarty P, Hennequart M, Pilley S, Hobor S, Hock AK, Walton JB, Morton JP, Gronroos E, Mason S, Yang M, McNeish I, Swanton C, Blyth K, Vousden KH. Cancer-Specific Loss of p53 Leads to a Modulation of Myeloid and T Cell Responses. Cell Rep. 2020 Jan 14;30(2):481-496.e6. doi: 10.1016/j.celrep.2019.12.028.
PubMed 31940491Vadakekolathu J, Lai C, Reeder S, Church SE, Hood T, Lourdusamy A, Rettig MP, Aldoss I, Advani AS, Godwin J, Wieduwilt MJ, Arellano M, Muth J, Yau TO, Ravandi F, Sweet K, Altmann H, Foulds GA, Stolzel F, Middeke JM, Ciciarello M, Curti A, Valk PJM, Lowenberg B, Gojo I, Bornhauser M, DiPersio JF, Davidson-Moncada JK, Rutella S. TP53 abnormalities correlate with immune infiltration and associate with response to flotetuzumab immunotherapy in AML. Blood Adv. 2020 Oct 27;4(20):5011-5024. doi: 10.1182/bloodadvances.2020002512.
PubMed 33057635Mussai F, De Santo C, Abu-Dayyeh I, Booth S, Quek L, McEwen-Smith RM, Qureshi A, Dazzi F, Vyas P, Cerundolo V. Acute myeloid leukemia creates an arginase-dependent immunosuppressive microenvironment. Blood. 2013 Aug 1;122(5):749-58. doi: 10.1182/blood-2013-01-480129. Epub 2013 Jun 3.
PubMed 23733335Sierra-Filardi E, Nieto C, Dominguez-Soto A, Barroso R, Sanchez-Mateos P, Puig-Kroger A, Lopez-Bravo M, Joven J, Ardavin C, Rodriguez-Fernandez JL, Sanchez-Torres C, Mellado M, Corbi AL. CCL2 shapes macrophage polarization by GM-CSF and M-CSF: identification of CCL2/CCR2-dependent gene expression profile. J Immunol. 2014 Apr 15;192(8):3858-67. doi: 10.4049/jimmunol.1302821. Epub 2014 Mar 17.
PubMed 24639350Hartwig T, Montinaro A, von Karstedt S, Sevko A, Surinova S, Chakravarthy A, Taraborrelli L, Draber P, Lafont E, Arce Vargas F, El-Bahrawy MA, Quezada SA, Walczak H. The TRAIL-Induced Cancer Secretome Promotes a Tumor-Supportive Immune Microenvironment via CCR2. Mol Cell. 2017 Feb 16;65(4):730-742.e5. doi: 10.1016/j.molcel.2017.01.021.
PubMed 28212753Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, Kaiser EA, Snyder LA, Pollard JW. CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature. 2011 Jun 8;475(7355):222-5. doi: 10.1038/nature10138.
PubMed 21654748Corzo CA, Condamine T, Lu L, Cotter MJ, Youn JI, Cheng P, Cho HI, Celis E, Quiceno DG, Padhya T, McCaffrey TV, McCaffrey JC, Gabrilovich DI. HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med. 2010 Oct 25;207(11):2439-53. doi: 10.1084/jem.20100587. Epub 2010 Sep 27.
PubMed 20876310Stromnes IM, Greenberg PD, Hingorani SR. Molecular pathways: myeloid complicity in cancer. Clin Cancer Res. 2014 Oct 15;20(20):5157-70. doi: 10.1158/1078-0432.CCR-13-0866. Epub 2014 Jul 21.
PubMed 25047706Sallman DA, McLemore AF, Aldrich AL, Komrokji RS, McGraw KL, Dhawan A, Geyer S, Hou HA, Eksioglu EA, Sullivan A, Warren S, MacBeth KJ, Meggendorfer M, Haferlach T, Boettcher S, Ebert BL, Al Ali NH, Lancet JE, Cleveland JL, Padron E, List AF. TP53 mutations in myelodysplastic syndromes and secondary AML confer an immunosuppressive phenotype. Blood. 2020 Dec 10;136(24):2812-2823. doi: 10.1182/blood.2020006158.
PubMed 32730593