Pacritinib vs. Hydroxyurea in Advanced Proliferative Chronic Myelomonocytic Leukemia
18 Years and older, Male and Female
PROSPERA (primary)
NCI-2026-00827
ABNL-MARRO 002
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.
Objectives
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.
Eligibility
- 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 × 10?/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 × 10?/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 × 10?/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.
Treatment Sites in Georgia
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