Pacritinib vs. Hydroxyurea in Advanced Proliferative Chronic Myelomonocytic Leukemia

NCT07033598 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: PROSPERAABNL-MARRO 002
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this clinical trial is to learn if pacritinib works better than hydroxyurea to treat advanced proliferative chronic myelomonocytic leukemia in adults. The main questions it aims to answer are:

• Does pacritinib improve disease control compared to hydroxyurea?
• What medical problems do participants have when taking pacritinib or hydroxyurea? Researchers will compare pacritinib to hydroxyurea to see if pacritinib is more effective and better tolerated in people with advanced proliferative chronic myelomonocytic leukemia. Participants will be randomly assigned to receive either pacritinib twice a day or hydroxyurea for up to 48 weeks. After treatment ends, participants will be followed for up to one year.

Conditions

Leukemia, Myelomonocytic, Chronic

Outcome Measures

Primary Outcomes (5)

• Clinical benefit at Week 24, defined as achieving erythroid response in the absence of leukemic transformation.

  For participants with baseline hemoglobin \<10 g/dL, response is defined as either a ≥1.5 g/dL hemoglobin increase lasting ≥8 weeks without red blood cell transfusion, or, if transfusion-dependent at baseline (≥4 units in the 8 weeks pre-enrollment), achieving ≥8 weeks of red blood cell transfusion independence, excluding transfusions given for pretreatment Hb ≤8.5 g/dL. Leukemic transformation is defined as ≥20% blasts or blast equivalents in the peripheral blood or bone marrow biopsy, or development of granulocytic sarcoma.

  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.

  For participants with baseline platelet counts \<100 × 10⁹/L, response is defined as one of the following: an increase to ≥20 × 10⁹/L and by ≥100% for ≥8 weeks without platelet transfusion (if baseline \<20 × 10⁹/L); an increase of ≥30 × 10⁹/L for ≥8 weeks without transfusion (if baseline 20-\<100 × 10⁹/L); or, if transfusion-dependent at baseline (≥4 units in the 8 weeks pre-enrollment), achieving ≥8 weeks of platelet transfusion independence. Leukemic transformation is defined as ≥20% blasts or blast equivalents in the peripheral blood or bone marrow biopsy, or development of granulocytic sarcoma.

  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.

  For participants with baseline ANC ≤1 × 10⁹/L, response is defined as either an increase to \>0.5 × 10⁹/L and by ≥100% for ≥8 weeks without myeloid growth factors (if baseline ANC ≤0.5 × 10⁹/L), or an increase by ≥50% for ≥8 weeks without myeloid growth factors (if baseline ANC \>0.5 to ≤1 × 10⁹/L). Leukemic transformation is defined as ≥20% blasts or blast equivalents in the peripheral blood or bone marrow biopsy, or development of granulocytic sarcoma.

  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.

  For participants with baseline spleen ≥5 cm below the left costal margin (midclavicular line), spleen response is defined as a ≥35% reduction in spleen volume at endpoint assessment by MRI or CT. Leukemic transformation is defined as ≥20% blasts or blast equivalents in the peripheral blood or bone marrow biopsy, or development of granulocytic sarcoma.

  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.

  Among participants with baseline Total Symptom Score (TSS) ≥20 per the MPN-SAF TSS: achieving ≥50% TSS reduction from baseline at the time of endpoint assessment. Leukemic transformation is defined as ≥20% blasts or blast equivalents in the peripheral blood or bone marrow biopsy, or development of granulocytic sarcoma.

  Measured from Week 24 through the end of treatment, up to 48 weeks.

Secondary Outcomes (12)

• Clinical benefit at any time, defined as achieving at least one of the primary endpoint clinical benefit response criteria at any time on study.

  Measured from the start of study treatment to the end of treatment, for up to 48 weeks.

• 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

  Measured from Week 24 through the end of treatment, up to 48 weeks.

• Duration of response for primary endpoint (clinical benefit by Week 24)

  Measured from Week 24 through the end of treatment, up to 48 weeks.

• Event-free survival

  Measured from the start of study treatment to the end of treatment, for up to 48 weeks.

• Leukemia-free survival, where events include death from any cause or transformation to AML (including granulocytic sarcoma)

  Measured from the start of study treatment to the end of treatment, for up to 48 weeks.

Study Arms (2)

Pacritinib

EXPERIMENTAL

Pacritinib 200 mg twice daily

Drug: Pacritinib

Hydroxyurea

ACTIVE COMPARATOR

Hydroxyurea at doses up to 4 g daily

Drug: Hydroxyurea

Interventions

Hydroxyurea DRUG

capsules or tablets

Hydroxyurea

Pacritinib DRUG

100-mg capsules

Pacritinib

Eligibility Criteria

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

You may qualify 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 may not qualify 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:

Sponsors & Collaborators

• Theradex: lead
• Sobi, Inc.: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: collaborator
• MDS/MPN International Working Group (UK Sponsor): collaborator

Study Sites (4)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Winship Cancer Institute at Emory

Atlanta, Georgia, 30322, United States

RECRUITING

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic

Interventions

11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene; Hydroxyurea

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Central Study Contacts

Zach Albaugh

CONTACT

zalbaugh@theradex.com

Melissa Fischer

CONTACT

mfischer@mdsmpn.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomization will be stratified by prior therapy. Within each stratum, participants will be randomly assigned to receive either pacritinib or hydroxyurea in a 2:1 ratio.

Study Record Dates

• First Submitted: June 5, 2025
• First Posted: June 24, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: March 5, 2026

Record last verified: 2026-03

Locations

US (4)