Axatilimab with or without azacitidine for adults with advanced myeloproliferative neoplasms or high‑risk CMML
Phase 1b/2 Study of Axatilimab (SNDX-6352) + Azacitidine (AZA) in Advanced Phase MPN, MPN/MDS Overlap or High-Risk CMML
This trial tests whether the antibody axatilimab, alone or together with the chemotherapy azacitidine, can help adults with advanced‑phase myeloproliferative neoplasms, MPN/MDS overlap, or high‑risk chronic myelomonocytic leukemia (CMML).
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 52 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Ohio State University Comprehensive Cancer Center Academic / other |
| Drugs / interventions | axatilimab, ruxolitinib, chemotherapy |
| Locations | 1 site (Columbus, Ohio) |
| Trial ID | NCT06523556 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Adults (≥18) with morphologically confirmed advanced‑phase MPN, MPN/MDS overlap, or intermediate‑2/high‑risk CMML who meet the protocol's newly diagnosed or relapsed/refractory cohort definitions and can consent and attend study visits are the intended participants.
Not a fit: Patients without these specified diagnoses, those who are medically unfit for investigational therapy, or those with uncontrolled severe infections or organ dysfunction are unlikely to benefit from participation.
Why it matters
Potential benefit: If effective, the regimen could reduce disease activity, lower transfusion needs, and potentially delay progression in patients with advanced MPNs or high‑risk CMML.
How similar studies have performed: Early‑phase trials combining targeted antibodies with azacitidine in myeloid malignancies have shown variable, limited activity, and the specific axatilimab plus azacitidine approach remains a relatively novel strategy under investigation.
Eligibility criteria
Show full inclusion / exclusion criteria
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) * 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: * Previous treatment for MPN or MDS/MPN overlap with chemotherapy or other antineoplastic agents including lenalidomide and hypomethylating agent (HMAs) such as decitabine or azacitidine or INQOVI (oral decitabine) (patients who had up to 2 cycles of hypomethylating agents \[HMAs\] can be included). However, previous treatment with hydroxyurea and/or ruxolitinib is permitted * 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 this trial is running
Columbus, Ohio
- Ohio State University Comprehensive Cancer Center — Columbus, Ohio, 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.