Atypical Chronic Myeloid LeukemiaPhase 1/2NCT06523556
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
A Phase 1/2 study testing Axatilimab, Azacitidine and Biospecimen Collection in people with Atypical Chronic Myeloid Leukemia and Chronic Myelomonocytic Leukemia, run by Uma Borate at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atypical Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic/Myeloproliferative Neoplasm
- What is being tested?
- Axatilimab, Azacitidine and Biospecimen Collection
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 49 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Aug 2024to 31 Oct 2028
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- Previous known allergy/sensitivity to components of axatilimab
- History of acute or chronic pancreatitis
- History of myositis
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
The Ohio State University Comprehensive Cancer Center contact
United States1 site, 1 recruiting
- Recruiting
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
Uma M. Borate, 614-293-3316, Uma.Borate@osumc.edu
Uma M. Borate
About this study
Official title: Phase 1b/2 Study of Axatilimab (SNDX-6352) + Azacitidine (AZA) in Advanced Phase MPN, MPN/MDS Overlap or High-Risk CMML
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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 the overall response rate of axatilimab + azacitidine (AZA) in newly diagnosed patients with advanced phase MPN, MPN/MDS overlap or high-risk CMML using Savona response criteria.
SECONDARY OBJECTIVES:
- Determine the safety and tolerability of axatilimab + azacitidine combination therapy in those with newly diagnosed advanced phase MPN, MPN/MDS overlap or high-risk CMML.
II. Determine the quality of life in patients receiving axatilimab + AZA using a Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPNSAF).
III. Determine the effect of axatilimab + azacitidine on symptom relief which will be measured by transfusion burden (platelet and/or packed red blood cell), time in hospital, and immune related side effects specifically reactivation of tuberculosis (TB), infusion-related reactions, hepatotoxicity, pneumonia, pyrexia, sepsis, shortness of breath (SBO), hemoptysis, periorbital edema, fatigue, and pancreatitis.
EXPLORATORY OBJECTIVES:
- To assess the pharmacokinetics of axatilimab in combination with AZA. II. To describe the prevalence and trajectories of patients' physical activity during treatment.
III. To perform detailed correlative studies related to genetic, biochemical, and immunologic changes that occur with axatilimab in combination with AZA.
OUTLINE: This is a phase I, dose-escalation study of axatilimab followed by a phase II study.
PHASE I: Patients receive axatilimab intravenously (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.
PHASE II: Patients receive axatilimab IV over 30 minutes on days 1 and 15 and azacitidine IV over 10-40 minutes or subcutaneously (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 partial response (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.
After completion of study treatment, patients are followed up at 30 days and then every 6 months for up to 24 months after last dose of study medication.
- Conditions
- Atypical Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic/Myeloproliferative Neoplasm, Recurrent Myelodysplastic/Myeloproliferative Neoplasm, Recurrent Myeloproliferative Neoplasm, Refractory Chronic Myelomonocytic Leukemia
- Being tested
- Axatilimab, Azacitidine, Biospecimen Collection, Bone Marrow Aspiration and Biopsy, Survey Administration
- Medical subject headings
- Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Leukemia, Myelomonocytic, Chronic, Myelodysplastic-Myeloproliferative Diseases, Myeloproliferative Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AxatilimabBiological
Also called Anti-M-CSFR Monoclonal Antibody SNDX-6352, SNDX 6352, SNDX-6352, SNDX6352
Given IV
AzacitidineDrug
Also called 5 AZC, 5-AC, 5-Azacitidine, 5-Azacytidine
Given IV or SC
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo blood sample collection
Bone Marrow Aspiration and BiopsyProcedure or surgery
Undergo bone marrow biopsy and aspiration
Survey AdministrationOther
Ancillary study
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: Axatilimab; Drug: Azacitidine; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Other: Survey Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of dose limiting toxicities
Includes hematologic and non-hematologic toxicities
Measured: 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.
Measured: Up to 5 years
Secondary outcomes (5)
Incidence of adverse events
Adverse events will be tabulated by toxicity grade and relationship with study medication and assessed by Common Terminology Criteria for Adverse Events version 5.0.
Measured: Up to 30 days after end of treatment
Quality of life measured by Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPNSAF)
Will be assessed in patients receiving axatilimab + azacitidine (AZA) and will be determined using a Modified Myeloproliferative Neoplasm Symptom Assessment Form (MPNSAF) score. The MPNSAF score has a range from 0 to 100 with 100 representing the highest level of symptom severity. Descriptive statistics, means and standard deviations or medians and ranges will be applied to summarize the MPNSAF score.
Measured: Up to 5 years
Number of platelet transfusions
Will be assessed in patients receiving axatilimab + azacitidine and will be determined by descriptive statistics.
Measured: Up to 5 years
Number of packed red blood cell transfusions
Will be assessed in patients receiving axatilimab + azacitidine and will be determined by descriptive statistics.
Measured: Up to 5 years
Time in hospital
Will be assessed in patients receiving axatilimab + azacitidine and will be determined by descriptive statistics.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2024
- Study start2 Aug 2024
- Primary completion31 Oct 2027 (estimated)
- Study completion31 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Atypical Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 49 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Uma Borate
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Corporation
- Responsible party
- Sponsor-investigator, Uma Borate, Ohio State University Comprehensive Cancer Center
- Investigators
- Uma M Borate, MD, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06523556
- Sponsor's protocol ID
- OSU-23442
- Other IDs
- NCI-2024-05515
- Status last verified
- Aug 2026
- First submitted
- 9 Jul 2024
- Last updated
- 27 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No