Pacritinib versus Hydroxyurea for advanced proliferative chronic myelomonocytic leukemia

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• 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
• King's College Hospital, NHS Foundation Trust
  London, Greater London, United Kingdom Recruiting
• The Christie, NHS Foundation Trust
  Manchester, Greater Manchester, United Kingdom Recruiting

Study contacts

• Study coordinator: Zach Albaugh
• Email: zalbaugh@theradex.com

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Pacritinib Effectiveness in Real-world Settings

  This real-world study will see how pacritinib works for adults with myelofibrosis by looking back at medical records from several centers.

  Recruiting at 5 sites Swedish Orphan Biovitrum · New Haven, Connecticut and 4 other locations · NCT07774455

• Pacritinib and Selinexor in JAK-inhibitor naive myelofibrosis with anemia and low platelets

  This trial tests whether combining pacritinib and selinexor helps patients with myelofibrosis who have anemia and low platelets and have not yet tried a JAK inhibitor.

  Recruiting Phase 2 Icahn School of Medicine at Mount Sinai · Westwood, Kansas and 2 other locations · NCT07447817

• Pacritinib for bone marrow fibrosis in myelofibrosis with low platelets

  This trial will test if pacritinib can reduce bone marrow fibrosis and help restore blood counts in adults with myelofibrosis who have low platelets (50–120 × 10^9/L).

  Recruiting at 12 sites Phase 2 Grupo Español de Enfermedades Mieloproliferativas Crónicas PH Negativas · Barcelona, Barcelona and 12 other locations · NCT07394153

• Pacritinib for metastatic castration-resistant prostate cancer after ARSI

  This trial tests pacritinib in adults with metastatic castration-resistant prostate cancer that has progressed after ARSI treatment to see if the drug can help.

  Recruiting Phase 2 Medical College of Wisconsin · Milwaukee, Wisconsin · NCT07226713

• Pacritinib plus azacitidine or decitabine to help people with accelerated or blast‑phase myeloproliferative neoplasms reach stem cell transplant.

  This trial tests if adding pacritinib to standard azacitidine or decitabine helps adults with accelerated or blast‑phase myeloproliferative neoplasms get to allogeneic stem cell transplant.

  Recruiting Phase 2 University of Washington · Seattle, Washington · NCT07148947

• Pacritinib for relapsed or refractory Waldenström macroglobulinemia

  This trial will test whether the oral drug pacritinib can safely reduce disease and symptoms in adults whose Waldenström macroglobulinemia has returned or did not respond to prior treatment.

  Recruiting Phase 2 Dana-Farber Cancer Institute · Boston, Massachusetts · NCT06986174

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.