Pacritinib vs. Hydroxyurea in Advanced Proliferative Chronic Myelomonocytic Leukemia
ConditionLeukemia, Myelomonocytic, Chronic
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorTheradex
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
Pacritinib
Drug100-mg capsules
Hydroxyurea
Drugcapsules or tablets
Treatment groups
66 Participants
are divided into 2 treatment groupsGroup A: PacritinibExperimental treatment 1 intervention
Group B: HydroxyureaActive comparator 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Measured from Week 24 through the end of treatment, up to 48 weeks.2
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.
Time frame
Measured from Week 24 through the end of treatment, up to 48 weeks.3
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.
Time frame
Measured from Week 24 through the end of treatment, up to 48 weeks.4
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.
Time frame
Measured from Week 24 through the end of treatment, up to 48 weeks.Secondary outcomes
1
Clinical benefit at any time, defined as achieving at least one of the primary endpoint clinical benefit response criteria at any time on study.
Time frame
Measured from the start of study treatment to the end of treatment, for up to 48 weeks.2
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
Time frame
Measured from Week 24 through the end of treatment, up to 48 weeks.3
Duration of response for primary endpoint (clinical benefit by Week 24)
Time frame
Measured from Week 24 through the end of treatment, up to 48 weeks.4
Event-free survival
Event-free survival is defined as the time without death from any cause, transformation to AML (including granulocytic sarcoma), or disease progression after ≥3 cycles (Week 12), including CMML-1 to CMML-2 with ≥5% absolute blast increase or worsening splenomegaly.
Time frame
Measured from the start of study treatment to the end of treatment, for up to 48 weeks.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Theradex
Lead sponsor
MDS/MPN International Working Group (UK Sponsor)
Collaborator
Sobi, Inc.
Collaborator
H. Lee Moffitt Cancer Center and Research Institute
Collaborator
Source ClinicalTrials.gov