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) in patients with a low platelet count

Phase 1

Conditions: Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis with Thrombocytopenia
MedDRA version: 18.1Level: PTClassification code 10028537Term: MyelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-004000-19-GB

Lead Sponsor: CTI BioPharma Corp.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 311

Inclusion Criteria

1. Intermediate-1 or -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 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 old
7. ECOG performance status 0 to 3
8. Peripheral blast count <10%
9. Absolute neutrophil count (ANC) >500/µL
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 x 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 outcomes instrument
19. 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 170
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 130

Exclusion Criteria

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 pacritinib
4. There is no maximum cumulative prior JAK2 inhibitor treatment (approved or investigational)
5. Completed allogeneic stem cell transplantation (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’s 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 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 >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 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 clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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