Status:

RECRUITING

Axatilimab With or Without Azacitidine for the Treatment of Patients With Advanced Phase Myeloproliferative Neoplasms, Myeloproliferative Neoplasm/Myelodysplastic Syndrome Overlap or High Risk Chronic Myelomonocytic Leukemia

Lead Sponsor:

Uma Borate

Collaborating Sponsors:

Incyte Corporation

Conditions:

Atypical Chronic Myeloid Leukemia

Chronic Myelomonocytic Leukemia

Eligibility:

All Genders

18+ years

Phase:

PHASE1

PHASE2

Brief Summary

This phase Ib/II trial tests the best dose of axatilimab and effectiveness of axatilimab with or without azacitidine for the treatment of patients with advanced phase myeloproliferative neoplasms (MPN...

Detailed Description

PRIMARY OBJECTIVES: I. To determine the recommended phase 2 dose (RP2D) of axatilimab in relapsed or refractory patients with advanced phase MPN, MPN/MDS overlap or high-risk CMML. II. To evaluate t...

Eligibility Criteria

Inclusion

  • 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

  • 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

Key Trial Info

Start Date :

August 2 2024

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

December 31 2026

Estimated Enrollment :

52 Patients enrolled

Trial Details

Trial ID

NCT06523556

Start Date

August 2 2024

End Date

December 31 2026

Last Update

June 26 2025

Active Locations (1)

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1

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States, 43210