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Not yet recruiting NCT07511062

Axatilimab Combined With Decitabine/Venetoclax for the Treatment of TP53-mutated AML

Phase I Interventional Acute Myeloid Leukemia TP53 Gene Mutation

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Decitabine, Venetoclax, Axatilimab.
Who it may be relevant to
Registry conditions: Acute Myeloid Leukemia, TP53 Gene Mutation. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

Axatilimab Combined With Decitabine/Venetoclax for the Treatment of TP53-mutated/Deleted AML Patients

Overview

Axatilimab combined with Decitabine/Venetoclax for the treatment of TP53-mutated/deleted AML patients

Interventions

  • Drug Decitabine
    20mg/m2/d x5 days (induction \& consolidation)
  • Drug Venetoclax
    400mg/d x14 days (induction); 400mg/d x7 days (consolidation)
  • Drug Axatilimab
    Dose escalation, given on Days 1 and 15 of each cycle

Primary outcome measures

  • Phase 2 Dose Level determination [Time frame: 1 year]
  • Estimation of MRD-negative complete remission [Time frame: 2 months]
Secondary outcome measures (4)
  • Estimation of Response Rates, Overall Survival [Time frame: 1 year]
  • Evaluation of Safety of the Regimen [Time frame: 1 year]
  • Estimation of Progression Free Survival [Time frame: 1 year]
  • Estimation of Overall Survival [Time frame: 1 year]

Eligibility criteria

Inclusion criteria

  • 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)

Exclusion criteria

  • 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
  • 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Single group
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 1 center
  • Northside Hospital, Inc. — Atlanta

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/NEJM PMID 39292927
  • 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
  • Alexander 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 PMID 25157821
  • Lemmon 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. PMID 20602996
  • Rosnet O, Birnbaum D. Hematopoietic receptors of class III receptor-type tyrosine kinases. Crit Rev Oncog. 1993;4(6):595-613. PMID 7506935
  • Xu 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. PMID 35030341
  • Blagih 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. PMID 31940491
  • Vadakekolathu 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 wit PMID 33057635

Identifiers

NCT: NCT07511062 · NSH 1436

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗