Pacritinib versus Hydroxyurea for advanced proliferative chronic myelomonocytic leukemia

A Randomized Phase 2 Study of Pacritinib vs. Hydroxyurea in Patients With Advanced Proliferative Chronic Myelomonocytic Leukemia

This trial tests whether pacritinib works better than hydroxyurea for adults with advanced proliferative chronic myelomonocytic leukemia.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 66 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Theradex (Industry-sponsored)
• Drugs / interventions: pacritinib, chemotherapy
• Locations: 4 sites (Tampa, Florida and 3 other locations)
• Trial ID: NCT07033598 on ClinicalTrials.gov

What this trial studies

This is a randomized, multicenter, open-label Phase 2 trial comparing pacritinib 200 mg twice daily to physician-managed hydroxyurea in adults with advanced proliferative CMML. About 66 participants will be randomized 2:1 (pacritinib:hydroxyurea) after a 28-day screening period and treated for up to 48 weeks with follow-up including a 30-day post-treatment visit and survival monitoring for about one year. Randomization is stratified by prior therapy (hydroxyurea or hypomethylating agents versus none), and participants who do not derive benefit on pacritinib by Week 24 will discontinue while some hydroxyurea non-responders may switch to pacritinib if they meet safety criteria. Safety, disease control, overall survival, event-free survival, and transplant outcomes will be tracked during treatment and the follow-up periods.

Who should consider this trial

Good fit: Adults with CMML-1 (WHO), proliferative disease (WBC ≥13 × 10^9/L), and advanced features such as palpable splenomegaly, Total Symptom Score ≥20, or platelets <100 × 10^9/L, with ECOG ≤2 and adequate organ function are the intended participants.

Not a fit: Patients with non-proliferative CMML, marrow blasts ≥10% or peripheral blasts ≥5%, poor organ function, ECOG >2, or who cannot tolerate either study medication are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, pacritinib could offer better blood count and spleen control and improved symptom relief compared with hydroxyurea for people with proliferative CMML.

How similar studies have performed: Related agents including pacritinib have shown activity in other myeloid disorders like myelofibrosis, but randomized data specifically in proliferative CMML are limited, so this application is partially novel.

Eligibility criteria

Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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).

Where this trial is running

Tampa, Florida and 3 other locations

• Moffitt Cancer Center — Tampa, Florida, United States (Recruiting)
• Winship Cancer Institute at Emory — Atlanta, Georgia, United States (Recruiting)
• Mayo Clinic Rochester — Rochester, Minnesota, United States (Recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Zach Albaugh

Conditions Leukemia, Myelomonocytic, Chronic