Clinical Trial 23478

• Overview

  Study Title:

  PROSPERA: A Randomized Phase 2 Study of Pacritinib vs. Hydroxyurea in Patients with Proliferative Advanced CMML

  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.

  Objective:

  Primary Objective: To evaluate the efficacy of pacritinib compared to hydroxyurea (HU) in patients with advanced proliferative CMML. Secondary Objectives: To evaluate disease progression in participants with advanced proliferative CMML treated with pacritinib compared to HU. To evaluate safety and tolerability of pacritinib compared to HU in participants with advanced proliferative CMML.

• Treatments

  Therapies:

  Chemotherapy (NOS); JAK2/IRAK1/ACVR1 Inhibitor

  Medications:

  Hydroxyurea (Droxia); Pacritinib ()

• Inclusion Criteria

  Inclusion Criteria:
  • Diagnosis of CMML-1 (5th WHO classification), with > 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 > 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

  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).

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