Axatilimab mit oder ohne Azacitidin zur Behandlung von Patienten mit myeloproliferativen Neoplasien im fortgeschrittenen Stadium, Überlappung von myeloproliferativem Neoplasma und myelodysplastischem Syndrom oder chronischer myelomonozytärer Leukämie mit hohem Risiko

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