Phase I/II Clinical Trial of Axatilimab, a CSF1R Monoclonal Antibody, in Combination With Ruxolitinib as Therapy for Patients With Myelofibrosis (MF) and Chronic Myelomonocytic Leukemia (CMML)

NCT07128381 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2025-0621NCI-2025-05876
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

• To find the recommended dose of axatilimab given alone and in combination with ruxolitinib in patients with MF and CMML.
• To learn if axatilimab given in combination with ruxolitinib can help to control MF and CMML.

Conditions

Myelofibrosis (MF); Chronic Myelomonocytic Leukemia (CMML)

Outcome Measures

Primary Outcomes (1)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (1)

Monotherapy or Combination: Treatment with Axatilimab +/- Ruxolitinib IV Q4W

EXPERIMENTAL

Participants will self-administered approximately 12 hours apart without regard to food

Drug: Axatilimab (SNDX-6352); Drug: Ruxolitinib

Interventions

Axatilimab (SNDX-6352) DRUG

Taken orally

Monotherapy or Combination: Treatment with Axatilimab +/- Ruxolitinib IV Q4W

Ruxolitinib DRUG

Taken orally

Monotherapy or Combination: Treatment with Axatilimab +/- Ruxolitinib IV Q4W

Eligibility Criteria

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

You may qualify if:

• Age .18 years as MF and CMML are very rare diseases in the pediatric population.
• Diagnosis of MF by WHO or ICC and:
• Phase 1 dose escalation (Cohort A and B): at least 1 prior therapy for MF or with suboptimal response after at least 3 months of therapy with a JAK inhibitor.
• Phase 2 dose expansion:
• i. Relapsed cohort (Cohort C): Patients with at least 1 prior MF therapy. or ii. JAKi-naive cohort (Cohort D): patients with newly diagnosed and treatment naive MF with intermediate .1 risk by DIPSS-plus (Appendix 2)
• Diagnosis of CMML refractory to treatment with hydroxyurea (for patients with proliferative CMML defined as WBC.13x109/L) or at least 4 cycles of treatment with hypomethylating agent, with relapse/progression after any number of cycles of hypomethylating agent therapy or who are intolerant of treatment with either therapy. Patients may have received prior therapy with other investigational agents or cytotoxic regimens.
• ECOG performance status ≤2
• Adequate hepatic function with total bilirubin \</=3 x ULN, AST or A LT \</= 3xULN unless related to disease involvement.
• Serum creatinine clearance \>30mL/min and no end/stage renal disease (using Cockcroft-Gault).
• Prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg, G-CSF, GM-CSF, procrit, aranesp, thrombopoietin) is allowed at any time prior to cycle 1 day 1 of therapy.
• Patient (or patient's legally authorized representative) must have signed an informed consent document indicating that the patient understands the purpose of and procedures required for the study and is willing to participate in the study. Non-English speaking patients may be consented.
• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
• Postmenopausal (no menses in greater than or equal to 12 consecutive months).
• History of hysterectomy or bilateral salpingo-oophorectomy.

You may not qualify if:

• Patients who are currently receiving treatment for a malignancy (not including basal cell carcinoma, nonmelanoma skin cancer, cervical carcinoma in situ, early stage breast cancer or localized prostate cancer treated with hormone therapy). Patients with history of other cancers should be free of disease for at least 2 years prior to the Screening Visit or not requiring active treatment at the time of enrollment.
• Patients who are receiving any other investigational agents or with prior CSF1-R inhibitor therapy.
• Active, uncontrolled bacterial, fungal, parasitic, or viral infection. Infections are considered controlled if appropriate therapy has been initiated and, at the time of screening, there is no evidence of infection worsening, such as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs, or radiographic findings attributable to infection.
• Patients with evidence of active or latent tuberculosis. Prior to enrollment, patients should be evaluated for tuberculosis risk factors, and those at higher risk should be tested for latent infection. Risk factors include, but are not limited to, prior residence in or travel to countries with a high prevalence of tuberculosis, close contact with a person with active tuberculosis, and a history of active or latent tuberculosis where an adequate course of treatment cannot be confirmed.
• Patients who have a known malabsorption syndrome or other condition that may impair absorption of study medication (e.g., gastrectomy).
• History of acute or chronic pancreatitis.
• Active symptomatic myositis.
• Platelet count \<50x109/L prior to enrollment and treatment initiation (for ruxolitinib combination cohorts only) except if related to either treatment for MF or CMML or treatment with cytotoxic therapy for any other reason.
• Pregnant women are excluded from this study because axatilimab and ruxolitinib are agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued if the mother is treated on study. These potential risks may also apply to other agents used in this study.
• Patients with reproductive potential who are unwilling to following contraception requirements (including condom use for males with sexual partners, and for females: prescription oral contraceptives \[birth control pills\], contraceptive injections, intrauterine devices \[IUD\], doublebarrier method \[spermicidal jelly or foam with condoms or diaphragm\], contraceptive patch, or surgical sterilization) throughout the study.
• Female patients with reproductive potential who do not have a negative urine or blood betahuman chorionic gonadotropin (beta HCG) pregnancy test at screening.
• Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy within 7 days of therapy initiation.
• Patients with history of chronic hepatitis B or C, irrespective of surface antigen or viral load detection given risk of viral reactivation with JAK inhibitor therapy.
• Patients with history of HIV given risk of JAK inhibitor-related immune-suppression.
• New York Heart Association (NYHA) Class III or IV congestive heart failure or LVEF \<50 by echocardiogram or multigated acquisition (MUGA) scan.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Incyte, Inc: collaborator

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Primary Myelofibrosis; Leukemia, Myelomonocytic, Chronic

Interventions

axatilimab; ruxolitinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Naveen Pemmaraju, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Naveen Pemmaraju, MD

CONTACT

(713) 792-4956; npemmaraju@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2025
• First Posted: August 19, 2025
• Study Start: January 2, 2026
• Primary Completion (Estimated): July 31, 2031
• Study Completion (Estimated): July 31, 2033
• Last Updated: January 5, 2026

Record last verified: 2026-01

Locations

US (1)