Axatilimab with or without azacitidine for adults with advanced myeloproliferative neoplasms or high‑risk CMML

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase Ib/II trial first identifies the recommended phase 2 dose of axatilimab in relapsed or refractory advanced‑phase MPN, MPN/MDS overlap, or high‑risk CMML, then evaluates the combination of axatilimab plus azacitidine in newly diagnosed patients. Axatilimab is a monoclonal antibody designed to block cell-surface proteins thought to support malignant white blood cell growth, while azacitidine is an antimetabolite that slows cancer cell proliferation. Participants receive assigned drug regimens with serial clinical assessments, bone marrow biopsies, biospecimen collection, and pharmacokinetic sampling, and responses are measured using Savona criteria. Secondary and exploratory measures include safety and tolerability, quality of life, transfusion burden, hospitalization time, pharmacokinetics, and correlative genetic and immune studies.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Signed informed consent must be obtained prior to participation in the study
* Age ≥ 18 years at the date of signing the informed consent form (ICF)
* Morphologically confirmed diagnosis of the following based on 2016 World Health Organization (WHO) classification (Arber et al 2016): Phase 1b, patients with relapsed or refractory of any of the following; phase 2, patients with newly diagnosed of any of the following:

  * Chronic myelomonocytic leukemia (CMML), classified as intermediate-2, OR high-risk per the CMML Specific Prognostic Scoring System (CPSS) Molecular Model
  * Atypical chronic myelocytic leukemia (aCML)
  * MDS/MPN unclassified (MDS/MPN-U)
  * Myeloproliferative neoplasm accelerated phase (MPN-AP)
  * MPN-AP requires a previous diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), or primary myelofibrosis (PMF) with intermediate-2 or high risk disease according to International Prostate Symptom Score (IPSS) as well as progression on or failure to respond to at least one line of therapy.
  * Myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) or MDS/MPN with SF3B1 mutation and thrombocytosis (MDS/MPN-SF3B1-T).
  * Not suitable for immediate myeloablative/intensive chemotherapy based on investigator assessment of age, comorbidities, local guidelines, institutional practice (any or all of these)
* PHASE Ib (RELAPSE \[R\]/ REFRACTORY \[R\]): Relapse/refractory patients who have received at least two cycles of disease directed therapy (prior therapies can include hypomethylating agents \[HMAs\], HMA combination therapies, and other disease directed therapies)
* PHASE II (NEWLY DIAGNOSED PHASE): Newly diagnosed patients without prior treatment, including intensive induction chemotherapy. However, previous treatment with hydroxyurea, ruxolitinib, and/or up to 2 cycles of HMAs (decitabine, azacitidine, oral decitabine \[INQOVI\]) is permitted
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × upper limit of normal (ULN)
* Total bilirubin ≤ 1.5 × ULN (except in the setting of isolated Gilbert syndrome)
* Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m\^2 (estimation based on Modification of Diet in Renal Disease \[MDRD\] formula, by local laboratory)
* Patient is able to communicate with the investigator and has the ability to comply with the requirements of the study procedures
* Women of childbearing potential and men, if not surgically sterilized, should use adequate contraception from 14 days prior to study entry and until 90 days after the last follow-up visit. Adequate contraception is defined as using hormonal contraceptives or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm or cervical cap, or a condom

Exclusion Criteria:

* Diagnosis of acute myeloid leukemia (AML) including acute promyelocytic leukemia and extra-medullary AML based on WHO 2016 classification (Arber et al 2016)
* Patients who are candidates for myeloablative or intensive chemotherapy treatment or who do not provide consent for this treatment
* History of organ transplant or allogenic hematopoietic stem cell transplant
* Participants with prior malignancy, except:

  * Participants with history of adequately treated malignancy for which no anticancer systemic therapy (namely chemotherapy, radiotherapy or surgery) is ongoing or required during the course of the study.
  * Participants who are receiving adjuvant therapy such as hormone therapy are eligible. However, participants who developed therapy related neoplasms are not eligible
* Previous known allergy/sensitivity to components of axatilimab
* History of acute or chronic pancreatitis
* History of myositis

Where it's running

• Ohio State University Comprehensive Cancer Center
  Columbus, Ohio, United States Recruiting
• Oregon Health & Science University
  Portland, Oregon, United States Recruiting

Study contacts

• Principal investigator: Uma M Borate, MD — Ohio State University Comprehensive Cancer Center
• Study coordinator: The Ohio State University Comprehensive Cancer Center
• Email: OSUCCCClinicaltrials@osumc.edu
• Phone: 800-293-5066

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Onvansertib treatment for recurrent or refractory chronic myelomonocytic leukemia and related conditions

  This study is testing a new drug called onvansertib to see if it can help people with recurring chronic myelomonocytic leukemia and related blood disorders feel better and respond to treatment.

  Recruiting Phase 1 Mayo Clinic · Rochester, Minnesota · NCT05549661

• Combining azacitidine, venetoclax, and gilteritinib for treating FLT3-mutated blood cancers

  This study is testing a new combination of three medications to see if they can help people with certain types of blood cancers that have a specific genetic mutation.

  Recruiting Phase 1/2 M.D. Anderson Cancer Center · Houston, Texas · NCT04140487

• Using hyperbaric oxygen therapy with stem cell transplants

  This study is testing whether hyperbaric oxygen therapy can help patients with chronic leukemias and myelofibrosis who are getting stem cell transplants feel better and recover more effectively.

  Recruiting Early Phase 1 University of Rochester · Rochester, New York · NCT03964506

• Testing STX-0712 in patients with advanced blood cancers

  This study is testing a new drug called STX-0712 to see if it can help people with advanced blood cancers like chronic myelomonocytic leukemia and acute myeloid leukemia who have run out of other treatment options.

  Recruiting at 6 sites Phase 1 Solu Therapeutics, Inc · Stanford, California and 6 other locations · NCT06950034

• Treatment of low or intermediate-risk myelodysplastic syndromes and chronic myelomonocytic leukemia with canakinumab

  This study is testing if a new medication called canakinumab can help people with low or intermediate-risk myelodysplastic syndromes and chronic myelomonocytic leukemia feel better and reduce their need for blood transfusions.

  Recruiting Phase 2 M.D. Anderson Cancer Center · Houston, Texas · NCT04239157

• Using edetate calcium disodium or succimer to treat acute myeloid leukemia or myelodysplastic syndrome during chemotherapy

  This study is testing whether two drugs, edetate calcium disodium and succimer, can safely help people with acute myeloid leukemia or myelodysplastic syndrome feel better during chemotherapy.

  Recruiting Phase 1 M.D. Anderson Cancer Center · Houston, Texas · NCT03630991

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.