A Randomized Controlled Phase 3 Study of Oral Pacritinib versus Best Available Therapy in Patients with Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis
- Conditions
- myelofibrosismyeloproliferative diseases10018849
- Registration Number
- NL-OMON41280
- Lead Sponsor
- CTI BioPharma Corp.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 30
1). Intermediate 1 or 2 or high-risk PMF, PPV-MF, or PET-MF (Passamonti et al 2010)
2). Palpable splenomegaly * 5 cm below LCM in midclavicular line by physical examination
3). Total Symptom Score (TSS) * 13 on the MPN-SAF-TSS2.0, not including te inactivity question.
4). Age * 18 years old
5). ECOG performance status 0-3
6). Peripheral blast count < 10%
7). Absolute neutrophil count > 500/*L
8). Patients who are platelet or red blood cell transfusion-dependent are eligible
9). 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 x ULN, and creatinine * 2.5 mg/dL
10). At least 6 months from prior splenic irradiation
11). At least 12 months from prior 32P therapy
12). At least 1 week since prior treatment (most recent dose) with a potent CYP3A4 inhibitor
13). At least 4 weeks since any experimental treatment for PMF, PPV-MF, or PET-MF
14). At least 2 weeks since any treatment for PMF, PPV-MF, or PET-MF
15). If fertile, both males and females must agree to use effective birth control. Women of childbearing potential must use highly effective methods (defined as those resulting in a failure rate of <1% per year when used consistently and correctly) for the duration of study treatment and for 12 months after last dose of study drug. The contraceptive methods considered highly effective are intrauterine devices and hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices, or injections
with prolonged release).
16). Willingness to undergo and ability to tolerate frequent MRI or CT assessments on study
17). Ability to understand and willingness to complete symptom assessments using a patient reported outcomes instrument
18). Ability to understand and willingness to sign the informed consent form
1). Any GI or metabolic condition that could interfere with absorption of oral medication
2). Life expectancy < 6 months
3). Prior treatment with a JAK2 inhibitor
4). Completed ASCT or eligible and willing to complete ASCT
5). History of splenectomy or planning to undergo splenectomy
6). Uncontrolled intercurrent illness, including but not limited to ongoing active infection or psychiatric illness or social situation that the treating physician judges would limit compliance with study requirements
7). Other malignancy within 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
8). Inflammatory or chronic functional bowel disorder such as Crohn disease, inflammatory
bowel disease, chronic diarrhea, or constipation
9). Clinically symptomatic and uncontrolled cardiovascular disease
10). History of myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure within 6 months prior to study randomization
11). New York Heart Association Class II, III, or IV congestive heart failure
12). Patients with CTCAE grade 2 cardiac dysrhythmias may be considered for inclusion, with approval of the medical monitor, if the arrhythmias are stable, aymptomatic and unlikely to affect patient safety. Ongoing cardiac dysrythmias of CTCAE * grade 3, corrected QTc prolongation > 450 ms or other factors that increase the risk for QT prolongation (eg, heart failure, serum potassium < 3.0 mEq/L, family history of long QT interval syndrome) are excluded.
13). Erythropoietic agent within 28 days prior to randomization
14). Thrombopoietic agent within 14 days prior to randomization
15). Known seropositivity for HIV
16). Known active hepatitis A, B, or C
17). Women who are pregnant or lactating
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Study objective:<br /><br>Primary efficacy objective:<br /><br>- The proportion of patients achieving a * 35% reduction in spleen volume from<br /><br>baseline to Week 24 by MRI or CT.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The key secundary objective is the proportion of patients with 50% reduction<br /><br>in total score from baseline to Week 24 on the Myeloproliferative Neoplasm<br /><br>Symptom Assessment Form (MPN-SAF TSS2.0).<br /><br><br /><br>Other secundary objectives are:<br /><br>- Proportion of patients with a baseline platelet count < 100,000/µL achieving<br /><br>> 35% reduction in spleen volume from baseline to Week 24 as measured by MRI or<br /><br>CT<br /><br>- Proportion of patients with a baseline platelet count < 100,000/µL achieving<br /><br>> 50% reduction in the TSS from baseline to Week 24<br /><br>- Proportion of patients with a baseline platelet count < 50,000/µL achieving ><br /><br>35% reduction in spleen volume from baseline to Week 24 as measured by MRI or CT<br /><br>- Proportion of patients with a baseline platelet count < 50,000/µL achieving ><br /><br>50% reduction in in the TSS from baseline to Week 24 </p><br>