Pacritinib vs. Hydroxyurea in Advanced Proliferative Chronic Myelomonocytic Leukemia

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Diagnosis of CMML-1 (5th WHO classification), with <10% bone marrow blasts on morphology and <5% peripheral blood blasts.
• Proliferative disease, defined as white blood cell count ≥13 × 10⁹/L.
• Advanced disease, defined as at least one of the following features during screening: spleen palpable ≥5cm below the lower costal margin in the midclavicular line; TSS ≥20; or platelet count <100 × 10⁹/L. For participants in whom spleen palpation is not feasible, an ultrasound exam may be performed for assessment of spleen craniocaudal length (length ≥12 cm by ultrasound is considered splenomegaly).
• ECOG performance status ≤2.
• Adequate organ function: AST and ALT ≤3 × ULN, total bilirubin ≤4 × ULN (≤8 × ULN in participants with Gilbert's syndrome), creatinine clearance >30 mL/min, absolute neutrophil count ≥0.5 × 10⁹/L, PT and PTT ≤1.5 × ULN.
• Women of child-bearing potential must have a negative serum pregnancy test within 7 days prior to enrollment and, along with male participants, must agree to use a highly effective method of contraception from the first dose through 90 days after the last dose.

You cannot join if

• Active malignancy diagnosed within the past 2 years, except for curatively treated non-invasive cancers (e.g., basal/squamous cell skin cancer, low-risk prostate cancer on stable endocrine therapy with PSA stable ≥3 months).
• Allogeneic hematopoietic stem cell transplant within 12 months prior to enrollment, or requiring immunosuppressive therapy within 6 months before enrollment.
• Likely to undergo allogeneic hematopoietic stem cell transplant within 6 months, per investigator assessment.
• Prior systemic treatment with any JAK inhibitor.
• Treatment with hypomethylating agents or cytotoxic chemotherapy (excluding hydroxyurea) within 28 days prior to enrollment.
• Participation in another interventional study or use of experimental therapy within 28 days or 5 half-lives, whichever is longer.
• Use of hematologic support drugs within 28 days prior to enrollment. Supportive care permitted.
• Use of strong CYP3A4 inhibitors or inducers within 14 days or 5 half-lives before enrollment, whichever is shorter.
• Use of systemic anticoagulants or antiplatelets (except aspirin ≤100 mg/day) within 14 days prior. Therapeutic anticoagulation allowed if stable for ≥90 days without bleeding events.
• CTCAE Grade ≥2 bleeding within 3 months prior to enrollment, unless due to a reversible cause (e.g., trauma, surgery).
• QTcF >450 ms (men) or >470 ms (women); QTcF up to 480 ms allowed if QRS >100 ms. QTcF may be repeated if affected by reversible factors.
• CTCAE Grade ≥3 cardiac event within 3 months before enrollment.
• Symptomatic heart failure with limitations on ordinary activity.
• Uncontrolled infection at study entry.
• Moderate/severe hepatic impairment (Child-Pugh B or C), or active viral hepatitis:
• HBV: Exclude if HBsAg+ or HBV DNA detectable. HBV antiviral therapy allowed if HBV DNA undetectable.
• HCV: Allowed if HCV Ab+ but RNA negative.
• Uncontrolled HIV or detectable viral load while on antiretrovirals.
• Known hypersensitivity to pacritinib or its excipients (microcrystalline cellulose, polyethylene glycol, magnesium stearate).

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

pacritinib citrate. The citrate salt form of pacritinib, an orally bioavailable inhibitor of Janus kinase 2 (JAK2), the JAK2 mutant JAK2V617F and FMS-like tyrosine kinase 3 (FLT3; CD135; STK1; FLK2), with potential antineoplastic activity. Upon oral administration of pacritinib citrate, pacritinib competes with JAK2 and the JAK2 mutant JAK2V617F for ATP binding, which may result in inhibition of JAK2 activation, inhibition of the JAK-signal transducer and activator of transcription (STAT) signaling pathway, and the induction of apoptosis. In addition, pacritinib targets, binds to and inhibits the activity of FLT3. This inhibits FLT3-mediated signaling and the proliferation of FLT3-expressing cancer cells. JAK2, often upregulated or mutated in a variety of cancer cells, plays a key role in tumor cell proliferation and survival. The JAK2V617F gain-of-function mutation involves a valine-to-phenylalanine modification at position 617. The JAK-STAT signaling pathway is a major mediator of cytokine activity. FLT3, a class III receptor tyrosine kinase (RTK), is overexpressed or mutated in most B-lineage neoplasms and in acute myeloid leukemias. In addition, JAK2 and FLT3 play a key role in the regulation of the inflammatory response and dendritic cell (DC) proliferation, differentiation and function. Inhibition of JAK2- and FLT3-mediated signaling may suppress the generation and differentiation of DCs, and may regulate inflammatory and immune responses. NCI Drug Dictionary

hydroxyurea. A monohydroxyl-substituted urea (hydroxycarbamate) antimetabolite. Hydroxyurea selectively inhibits ribonucleoside diphosphate reductase, an enzyme required to convert ribonucleoside diphosphates into deoxyribonucleoside diphosphates, thereby preventing cells from leaving the G1/S phase of the cell cycle. This agent also exhibits radiosensitizing activity by maintaining cells in the radiation-sensitive G1 phase and interfering with DNA repair. NCI Drug Dictionary

Treatments listed in the registry

• Pacritinib (Drug): 100-mg capsules
• Hydroxyurea (Drug): capsules or tablets

Randomized · Parallel · masking: None

Main goals

• Clinical benefit at Week 24, defined as achieving erythroid response in the absence of leukemic transformation. (Measured from Week 24 through the end of treatment, up to 48 weeks.)
• Clinical benefit at Week 24, defined as achieving platelet response in the absence of leukemic transformation. (Measured from Week 24 through the end of treatment, up to 48 weeks.)
• Clinical benefit at Week 24, defined as achieving neutrophil response in the absence of leukemic transformation. (Measured from Week 24 through the end of treatment, up to 48 weeks.)
• Clinical benefit at Week 24, defined as achieving spleen response in the absence of leukemic transformation. (Measured from Week 24 through the end of treatment, up to 48 weeks.)
• Clinical benefit at Week 24, defined as achieving symptom response in the absence of leukemic transformation. (Measured from Week 24 through the end of treatment, up to 48 weeks.)

Other goals

• Clinical benefit at any time, defined as achieving at least one of the primary endpoint clinical benefit response criteria at any time on study.
• Achieving response at Week 24 and 48 according to the IWG 2015 criteria), including the following subtypes: complete response, complete cytogenetic remission, partial remission, marrow response
• Duration of response for primary endpoint (clinical benefit by Week 24)
• Event-free survival
• Leukemia-free survival, where events include death from any cause or transformation to AML (including granulocytic sarcoma)
• Overall survival
• Incidence of allogeneic hematopoietic stem cell transplant.
• Adverse events and laboratory abnormalities as graded by NCI CTCAE v5.0.
• Change in arterial blood pressure measured in mmHg.
• Change in pulse rate measured in beats per minute.
• Change in respiratory rate measured in breaths per minute.
• Change in corrected QT interval measured in milliseconds using 12-lead electrocardiogram.

Planned enrollment: 66 (estimated).

• Moffitt Cancer Center, Tampa, Florida
• Winship Cancer Institute at Emory, Atlanta, Georgia
• Mayo Clinic Rochester, Rochester, Minnesota
• MD Anderson Cancer Center, Houston, Texas

2 recruiting sites outside the US. Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07033598
• NCI Drug Dictionary: C185891
• NCI Drug Dictionary: C560

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Aug 17, 2026. Public record; not medical advice.