A Randomized Controlled Phase 3 Study of Oral Pacritinib versus Best Available Therapy in Patients with Thrombocytopenia and Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis
- Conditions
- Myelofibrosis and myeloproliferative diseases1001884910018865
- Registration Number
- NL-OMON40900
- Lead Sponsor
- CTI BioPharma Corp.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 10
1. Intermediate-1, intermediate -2, or high risk PMF, PPV-MF, or PET-MF
2. Thrombocytopenia (platelet count * 100,000/µL) at any time after signing informed consent
3. Informed consent may be signed up to 35 days prior to randomization
4. Palpable splenomegaly *5 cm below the lower costal margin (LCM) in midclavicular line by physical examination
5. Total Symptom Score (TSS) *13 on the MPN-SAF TSS 2.0, not including the inactivity question
6. Age *18 years
7. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3
8. Peripheral blast count <10%
9. Absolute neutrophil count (ANC) >500/*L
10. Patients who are platelet or RBC transfusion dependent are eligible
11. Adequate liver and renal function, defined by liver transaminases (AST/SGOT and ALT/SGPT)
*3 × ULN (AST/ALT *5 × ULN if transaminase elevation is related to MF), direct bilirubin
*4 × ULN, and creatinine *2.5 mg/dL
12. At least 6 months from prior splenic irradiation
13. At least 12 months from prior 32P therapy
14. At least 1 week since prior treatment (most recent dose) with a potent cytochrome P450 3A4
(CYP3A4) inhibitor
15. At least 2 weeks since receiving any treatment for PMF, PPV-MF, or PET-MF
16. If fertile, males and females must agree to use effective birth control methods during the study
17. Willing to undergo and able to tolerate frequent MRI or CT assessments during the study
18. Able to understand and willing to complete symptom assessments using a patient-reported outcome instrument
19. Able to understand and willing to sign the Informed Consent Form
1. Any gastrointestinal (GI) or metabolic condition that could interfere with absorption of oral
medication
2. Life expectancy less than 6 months
3. Prior treatment with more than 2 JAK2 inhibitors or with pacritinib
4. There is no maximum of cumulative prior JAK2 inhibitor treatment (approved or investigational)
5. Completed allogeneic stem cell transplant (ASCT), or are eligible for and willing to complete ASCT
6. History of splenectomy or planning to undergo splenectomy
7. Uncontrolled intercurrent illness, including but not limited to ongoing active infection, psychiatric
illness, or social situation that, in the judgment of the treating physician, would limit compliance with study requirements
8. Active bleeding requiring hospitalization during the screening period
9. Other malignancy within the last 3 years, other than curatively treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, organ-confined or treated nonmetastatic prostate cancer with negative prostate-specific antigen, in situ breast carcinoma after complete surgical resection, or superficial transitional cell bladder carcinoma
10. Inflammatory or chronic functional bowel disorder, such as Crohn disease, inflammatory bowel disease, chronic diarrhea, or constipation
11. Clinically symptomatic and uncontrolled cardiovascular disease
12. History of any of the following within 6 months prior to randomization: myocardial infarction,
severe/unstable angina, or symptomatic congestive heart failure
13. New York Heart Association Class III or IV congestive heart failure
14. Patients with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events
(CTCAE) grade 2 cardiac arrhythmias may be considered for inclusion, with the approval of the
medical monitor, if the arrhythmias are stable, asymptomatic, and unlikely to affect patient safety.
Patients will be excluded if they have ongoing cardiac dysrhythmias of CTCAE grade *3, corrected
QT interval (QTc) prolongation >450ms, or other factors that increase the risk for QT interval
prolongation (eg, heart failure, hypokalemia [defined as serum potassium <3.0mEq/L that is
persistent and refractory to correction], or family history of long QT interval syndrome).
15. Erythropoietic agent within 28 days prior to randomization
16. Thrombopoietic agent within 14 days prior to randomization
17. Known seropositivity for human immunodeficiency virus (HIV)
18. Known active hepatitis A, B, or C virus infection
19. Women who are pregnant or lactating
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The efficacy co-endpoints for this analysis are the proportion of patients<br /><br>achieving a * 35% reduction in spleen volume from baseline to Week 24, as<br /><br>measured by magnetic resonance imaging (MRI) or computed tomography (CT) scan<br /><br>and the proportion of patients achieving a * 50% reduction in total symptom<br /><br>score (TSS) from baseline to Week 24 as measured by the Myeloproliferative<br /><br>Neoplasm Symptom Assessment Form 2.0 (MPN-SAF TSS 2.0).</p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary objectives are:<br /><br><br /><br>1 To compare the efficacy of QD pacritinib with that of BAT, as assessed by the<br /><br>proportion of patients<br /><br>achieving a * 35% reduction in spleen volume from baseline to Week 24 by MRI or<br /><br>CT and the<br /><br>proportion of patients achieving a * 50% reduction in the TSS from baseline to<br /><br>Week 24 on the<br /><br>MPN-SAF TSS 2.0.<br /><br><br /><br>2 To compare the efficacy of BID pacritinib with that of BAT, as assessed by<br /><br>the proportion of patients<br /><br>achieving a * 35% reduction in spleen volume from baseline to Week 24 by MRI or<br /><br>CT and the<br /><br>proportion of patients achieving a * 50% reduction in the TSS from baseline to<br /><br>Week 24 on the<br /><br>MPN-SAF TSS 2.0.</p><br>