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

NCT06523556 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: OSU-23442NCI-2024-05515
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

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), myeloproliferative neoplasm/myelodysplastic syndrome (MPN/MDS) overlap or high risk chronic myelomonocytic leukemia (CMML). Axatilimab is an antibody that is cloned from a single white blood cell that is known to be able to recognize cancer cells and block a protein on the surface of the white blood cells that may be involved in cancer cell growth. By blocking the proteins, this may slow or halt the growth of the cancer. Azacitidine is in a class of medications called antimetabolites. It works by stopping or slowing the growth of cancer cells. Giving axatilimab with or without azacitidine may be safe and effective in treating patients with advanced phase MPN, MPN/MDS overlap or high risk CMML.

Conditions

Atypical Chronic Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm; Recurrent Myelodysplastic/Myeloproliferative Neoplasm; Recurrent Myeloproliferative Neoplasm; Refractory Chronic Myelomonocytic Leukemia; Refractory Myelodysplastic/Myeloproliferative Neoplasm; Refractory Myeloproliferative Neoplasm

Outcome Measures

Primary Outcomes (2)

• Incidence of dose limiting toxicities

  Includes hematologic and non-hematologic toxicities

  Up to 42 days after the first dose of study medication

• Overall response rate

  The number of participants whose best response (according to the 2006 International Working Group response criteria) over the efficacy analysis period is a complete response or partial response will be tallied to estimate the overall response rate and provide a 95% exact confidence interval, according to the Clopper-Pearson method.

  Up to 5 years

Secondary Outcomes (5)

• Incidence of adverse events

  Up to 30 days after end of treatment

• Quality of life measured by Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPNSAF)

  Up to 5 years

• Number of platelet transfusions

  Up to 5 years

• Number of packed red blood cell transfusions

  Up to 5 years

• Time in hospital

  Up to 5 years

Study Arms (2)

Phase I (Axatilimab)

EXPERIMENTAL

Patients receive axatilimab IV over 30 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. At time of phase Ib completion, patients with clinical improvement may transition to phase II. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.

Biological: Axatilimab; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy

Phase II (Axatilimab and azacitidine)

EXPERIMENTAL

Patients receive axatilimab IV over 30 minutes on days 1 and 15 and azacitidine IV over 10-40 minutes or SC on days 1-7 of each cycle. Cycles repeat every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who achieve PR or better may continue for up to 24 total cycles. Patients who achieve less than PR receive 2 additional cycles and, if PR or better is achieved, may complete up to 24 total cycles. Patients undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.

Biological: Axatilimab; Drug: Azacitidine; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Other: Survey Administration

Interventions

Axatilimab BIOLOGICAL

Given IV

Also known as: Anti-M-CSFR Monoclonal Antibody SNDX-6352, SNDX 6352, SNDX-6352, SNDX6352, UCB6352

Phase I (Axatilimab); Phase II (Axatilimab and azacitidine)

Azacitidine DRUG

Given IV or SC

Also known as: 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, U-18496, Vidaza

Phase II (Axatilimab and azacitidine)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Phase I (Axatilimab); Phase II (Axatilimab and azacitidine)

Bone Marrow Aspiration and Biopsy PROCEDURE

Undergo bone marrow biopsy and aspiration

Phase I (Axatilimab); Phase II (Axatilimab and azacitidine)

Survey Administration OTHER

Ancillary study

Phase II (Axatilimab and azacitidine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Uma Borate: lead
• Incyte Corporation: collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Leukemia, Myelomonocytic, Chronic; Myelodysplastic-Myeloproliferative Diseases; Myeloproliferative Disorders

Interventions

axatilimab; Azacitidine; Specimen Handling; Biopsy

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative

Study Officials

• Uma M Borate, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 9, 2024
• First Posted: July 26, 2024
• Study Start: August 2, 2024
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2028
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

US (1)