Pacritinib vs. Hydroxyurea in Advanced Proliferative Chronic Myelomonocytic Leukemia

NCT ID: NCT07033598

Last Updated: 2025-08-21

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-31
• Study Completion Date: 2028-12-31

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.

Detailed Description

This is a randomized, multicenter, open-label Phase 2 clinical trial evaluating the efficacy and safety of pacritinib compared to hydroxyurea in adult participants with advanced proliferative chronic myelomonocytic leukemia (CMML). Approximately 66 participants will be randomized in a 2:1 ratio to receive either pacritinib 200 mg twice daily (n=44) or hydroxyurea (n=22) for up to 48 weeks. Randomization will be stratified based on prior therapy (i.e., prior use of hydroxyurea or hypomethylating agents vs. no prior therapy).

The study includes:

• A 28-day screening period
• A 48-week treatment period
• A 30-day post-treatment follow-up
• A survival follow-up phase lasting approximately one year after randomization Participants receiving pacritinib who are not deriving benefit by Week 24, as assessed by the treating physician, will discontinue treatment. Participants in the hydroxyurea arm who are not deriving benefit by Week 24-or who experience non-leukemic disease progression-may switch to pacritinib for the remainder of the treatment period, provided they meet predefined "Safe to Switch" criteria.

Participants who discontinue study therapy due to toxicity, disease progression, or other protocol-defined criteria will enter survival follow-up to monitor overall survival, event-free survival, leukemic-free survival, and receipt of allogeneic hematopoietic stem cell transplant. Data will be collected at least every three months until death, hematopoietic stem cell transplant, or leukemic transformation.

An independent data monitoring committee will oversee safety, with the first review after enrollment of ~18 participants and subsequent reviews approximately every 6 months.

Conditions

Leukemia, Myelomonocytic, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pacritinib

Pacritinib 200 mg twice daily

Group Type: EXPERIMENTAL

Pacritinib

Intervention Type: DRUG

100-mg capsules

Hydroxyurea

Hydroxyurea at doses up to 4 g daily

Group Type: ACTIVE_COMPARATOR

Hydroxyurea

Intervention Type: DRUG

capsules or tablets

Interventions

Pacritinib

100-mg capsules

Intervention Type: DRUG

Hydroxyurea

capsules or tablets

Intervention Type: DRUG

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sobi, Inc.

INDUSTRY

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: collaborator

Theradex

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

ABNL-MARRO 002

Identifier Type: OTHER

Identifier Source: secondary_id

PROSPERA

Identifier Type: -

Identifier Source: org_study_id