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A study comparing current standard therapies with pacritinib taken by mouth for the treatment of myelofibrosis (either diagnosed alone or after polycythemia vera or essential thrombocytopenia)

Phase 1
Conditions
Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis
MedDRA version: 18.0Level: PTClassification code 10028537Term: MyelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2012-004239-21-GB
Lead Sponsor
CTI BioPharma Corp.
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
327
Inclusion Criteria

1). Intermediate -1 or -2 high-risk (Passamonti et al 2010) PMF, PPV-MF, or PET-MF (Tefferi and Vardiman 2008; Barosi et al 2008)
2). Palpable splenomegaly = 5 cm below the lower costal margin (LCM) in midclavicular line by physical examination
3). Total Symptom Score (TSS) = 13 on the MPN-SAF-TSS 2.0, not including the inactivity question
4). Age = 18 years old
5). ECOG performance status 0-3
6). Peripheral blast count < 10%
7). Absolute neutrophil count > 500/µL
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 cytochrome P450 3A4 (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, willing to use effective birth control methods during the study. 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 that are considered highly effective are intrauterine devices and hormonal contraceptives (contraceptive pills, implants, transdermal patches, hormonal vaginal devices, or injections with prolonged release). Males must use a condom for the duration of the study and for 90 days after the last dose of study treatment. When abstinence is used as a method of birth control, only true abstinence is acceptable, when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (calendar, ovulation, symptothermal, and post-ovulation methods) and withdrawal are not acceptable methods of contraception.
16). Willing to undergo and able to tolerate frequent MRI or CT assessments on study
17). Able to understand and willing to complete symptom assessments using a patient reported outcomes instrument
18). Able to understand and willing to sign the informed consent form
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 178
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 144

Exclusion Criteria

1). Any gastrointestinal 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 allogeneic stem cell transplantation (ASCT) or eligible for 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 any of the following, within 6 months prior to randomization: myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure
11). New York Heart Association Class II, III, or IV congestive heart failure
12). Patients with National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 4) 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 > 450 ms or other factors that increase the risk for QT prolongation (eg, heart failure, hypokalemia [defined as serum potassium < 3.0 mEq/L that is persistant and refractory to correction], or family history of long QT interval syndrome).
13). Erythropoietic agent within 28 days prior to randomization
14). Thrombopoietic agent within 14 days prior to randomization
15). Known seropositivity for human immunodeficiency virus (HIV)
16). Known active hepatitis A, B, or C virus infection
17). Women who are pregnant or lactating

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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