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)

Inclusion Criteria

• •Age .18 years as MF and CMML are very rare diseases in the pediatric population.
• •Diagnosis of MF by WHO or ICC and:
• •1. 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.
• •2. 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.
• •* Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following:
• •* Postmenopausal (no menses in greater than or equal to 12 consecutive months).
• •* History of hysterectomy or bilateral salpingo-oophorectomy.
• •* Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy).
• •* History of bilateral tubal ligation or another surgical sterilization procedure.
• •* Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
• •* Ability to understand and the willingness to sign a written informed consent document.