A Phase 2 Dose-Finding Study of Pacritinib in Myelofibrosis Patients
- Conditions
- Primary Myelofibrosis, Post-essential thrombocythemia myelofibrosis, Post polycythaemia vera myelofibrosisMedDRA version: 20.0Level: PTClassification code 10077161Term: Primary myelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)MedDRA version: 20.0Level: LLTClassification code 10074692Term: Post essential thrombocythaemia myelofibrosisSystem Organ Class: 100000012930MedDRA version: 20.0Level: LLTClassification code 10074691Term: Post polycythaemia vera myelofibrosisSystem Organ Class: 100000012930MedDRA version: 20.0Level: PTClassification code 10028537Term: MyelofibrosisSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2017-001772-28-ES
- Lead Sponsor
- CTI BioPharma Corp.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 165
1. PMF, PPV-MF, or PET-MF (as defined by Tefferi and Vardiman 2008)
2. DIPSS Intermediate-1, Intermediate -2, or High risk (Passamonti et al 2010)
3. Prior ruxolitinib treatment failure or intolerance as defined by:
a. Treatment for =6 months with inadequate efficacy response (any measure) in the judgement of the investigator
b. Treatment for =28 days complicated by either:
i. RBC transfusion
ii. NCI CTCAE grade =3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while being treated with a dosage of <20 mg BID
4. Palpable splenomegaly =5 cm below the lower costal margin (LCM) in the midclavicular line as assessed by physical examination
5. Platelet count of =100,000/µL at any time during the screening period and prior to first dose of pacritinib, including patients who are platelet transfusion-dependent
6. TSS of =10 on the MPN-SAF TSS 2.0
7. Age =18 years old
8. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
9. Peripheral blast count of <10%
10. Absolute neutrophil count of >500/µL
11. Adequate liver and renal function, defined by liver transaminases (aspartate aminotransferase [AST]/serum glutamic oxaloacetic transaminase [SGOT] and alanine aminotransferase [ALT]/serum glutamic pyruvic transaminase [SGPT]), =3 × the upper limit of normal (ULN) (AST/ALT =5 × ULN if transaminase elevation is related to MF), direct bilirubin =4× ULN, and creatinine =2.5 mg/dL
12. Adequate coagulation function, defined by prothrombin time (PT)/international normalized ratio (INR), partial thromboplastin time (PTT), or thrombin time (TT) of =1.5 × ULN
13. Left ventricular cardiac ejection fraction of =45% by echocardiogram or multigated acquisition (MUGA) scan
14. QTc interval of <450 ms as assessed by ECG and corrected by the Fredericia method
15. If fertile, willing to use effective birth control methods during the study
16. Willing to undergo and able to tolerate frequent MRI or CT assessments during the study
17. Able to understand and willing to complete symptom assessments using a patient-reported outcomes instrument
18. Provision of informed consent
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 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 55
1. Life expectancy <6 months
2. Completed ASCT or are eligible for and willing to complete ASCT
3. History of splenectomy or planning to undergo splenectomy
4. Splenic irradiation within the last 6 months
5. Previously treated with pacritinib
6. Treatment with anticoagulation or antiplatelet agents, except for aspirin dosages of =100 mg per day, within the last 2 weeks
7. Treatment with a potent cytochrome P450 (CYP450) inducer within the last 2 weeks
8. Treatment with medications that can prolong the QTc interval within the last 2 weeks
9. Significant recent bleeding history defined as NCI CTCAE grade =2 within the last 3 months, unless precipitated by an inciting event (e.g., surgery, trauma, injury)
10. Any history of CTCAE grade =2 non-dysrhythmia cardiac conditions within the last 6 months. Patients with asymptomatic grade 2 non-dysrhythmia cardiac conditions may be considered for inclusion, with the approval of the medical monitor, if stable and unlikely to affect patient safety.
11. New York Heart Association Class II, III, or IV congestive heart failure
12. Any history of CTCAE grade =2 cardiac dysrhythmias within the last 6 months. Patients with non-QTc CTCAE grade 2 cardiac dysrhythmias may be considered for inclusion, with the approval of the medical monitor, if the dysrhythmias are stable, asymptomatic, and unlikely to affect patient safety.
13. QTc prolongation >450 ms or other factors that increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia [defined as serum potassium <3.0 mEq/L that is persistent and refractory to correction], family history of long QT interval syndrome, or concomitant use of medications that may prolong QT interval)
14. Any gastrointestinal or metabolic condition that could interfere with absorption of oral medication
15. Inflammatory or chronic functional bowel disorder such as Crohn’s Disease, inflammatory bowel disease, chronic diarrhea, or constipation
16. 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
17. Uncontrolled intercurrent illness, including, but not limited to, ongoing active infection or psychiatric illness or social situation that, in the judgment of the treating physician, would limit compliance with study requirements
18. Known seropositivity for human immunodeficiency virus
19. Known active hepatitis A, B, or C virus infection
20. 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