Primary Myelofibrosis, Post-essential thrombocythemia myelofibrosis, Post polycythaemia vera myelofibrosis MedDRA version: 20.0 Level: PT Classification code 10077161 Term: Primary myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10074692
Conditions
Interventions
Product Name: Pacritinib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Pacritinib
CAS Number: 937272-79-2
Current Sponsor code
Sponsors
CTI BioPharma Corp.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. PMF, PPV-MF, or PET-MF (as defined by Tefferi and Vardiman 2008, Appendix 4) 2. DIPSS Intermediate-1, Intermediate -2, or High risk (Passamonti et al. 2010, Appendix 3) 3. Prior ruxolitinib treatment with failure to benefit or intolerance as defined by at least one of the following: a. Treatment for =3 months with inadequate efficacy response defined as 500/µL 10. 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 11. Adequate coagulation function, defined by prothrombin time (PT)/international normalized ratio (INR), partial thromboplastin time (PTT), or thrombin time (TT) of =1.5 × ULN 12. Left ventricular cardiac ejection fraction (LVEF) of =45% by echocardiogram or multigated acquisition (MUGA) scan 13. If fertile, willing to use effective birth control methods during the study 14. Willing to undergo and able to tolerate frequent MRI or CT assessments during the study 15. Able to understand and willing to complete symptom assessments using a patient-reported outcomes instrument 16. 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 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 90
Exclusion criteria
Exclusion criteria: 1. Life expectancy 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) 16. Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication 17. Active or uncontrolled Inflammatory or chronic functional bowel disorder such as Crohn’s Disease, inflammatory bowel disease, chronic diarrhea, or constipation 18. 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 19. Uncontrolled intercurrent illness, including, but not limited to, ongoing active infection or psychiatric illness or social situation that, in the judgment of the treatin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? To determine a recommended dosage of pacritinib for further clinical studies; Secondary Objective: ? To examine the dose–response relationship for efficacy, as measured by spleen volume reduction (SVR) using MRI (preferred) or CT and TSS using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score version 2.0 (MPN-SAF TSS 2.0) ? To examine the dose–response relationship for safety with a focus on AEs of interest ? To further characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of pacritinib ? To evaluate the long term efficacy and safety of pacritinib treatment ;Timepoint(s) of evaluation of this end point: The primary endpoint is measured at Weeks 12 and 24. ; Primary end point(s): The primary efficacy variable for dosage selection is the percent reduction in spleen volume from baseline. The primary safety measure for dosage selection is the percentage of patients with CTCAE grade =3 cardiac AEs (Standardized MedDRA Query [SMQ]), CTCAE grade =3 hemorrhage AEs (SMQ), CTCAE grade =4 thrombocytopenia toxicity (central laboratory based), or CTCAE grade =4 anemia toxicity (central laboratory based). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Other supportive measures for evaluation as part of the dose–response relationship include: the percentage of patients who achieve at least 35% reduction in spleen volume; % TSS reduction from baseline; and the percentage of patients with at least 50% reduction in TSS. All other safety data including AEs, death and clinical laboratory measures will be used as supportive measures for evaluation of pacritinib dose-safety relationship and for long term safety evaluation. Long term efficacy is evaluated using percent reduction in spleen volume from baseline as measured by MRI or CT, percent reduction in TSS from baseline, percent reduction in spleen length by physical exam and the patient global impression assessment. ; Timepoint(s) of evaluation of this end point: The secondary endpoint is measured at Weeks 12 and 24. To evaluate the long term efficacy and safety of pacritinib treatment follow up will continue every 3 months up to 2.5 years (with the exception of MRI/CT spleen assessment, which will only be followed up to 2 years and TSS assessment, which will only be followed up to 48 weeks). | — |
Countries
France, Germany, Hungary, Israel, Italy, Korea, Republic of, Netherlands, Poland, Romania, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs-Sarah H. Telzrow
CTI BioPharma Corp.
Outcome results
None listed