A Phase 2 Dose-Finding Study of Pacritinib in Myelofibrosis Patients

Phase 1

• Conditions: 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 Term: Post essential thrombocythaemia myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: LLT Classification code 10074691 Term: Post polycythaemia vera myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10028537 Term: Myelofibrosis System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-001772-28-HU
• Lead Sponsor: CTI BioPharma Corp.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-06-02
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 150

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 <10% spleen volume reduction by MRI or <30% decrease from baseline in spleen length by physical examination or regrowth to to these parameters following an initial response; and/or
b. Treatment for =28 days complicated by either:
i. Development of a red blood cell transfusion requirement (at least 2 units/month for 2 months)
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. TSS of =10 on the MPN-SAF TSS 2.0 patients with a single symptom score of =5 or two symptoms =3 including only the symptoms of left upper quadrant pain, bone pain, itching or night sweats (Appendix 3)

6. Age =18 years old

7. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 (Appendix 6)

8. Peripheral blast count of <10% throughout the screening period

9. Absolute neutrophil count of >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

1. Life expectancy <6 months

2. Completed allo-SCT or are eligible for and willing to complete allo-SCT

3. History of splenectomy or planning to undergo splenectomy

4. Splenic irradiation within the last 6 months

5. Previously treated with pacritinib

6. Patients receiving high-dose ruxolitinib (more than 10 mg BID or 20
mg QD) who cannot tolerate tapering down ruxolitinib to 10 mg BID or
less prior to the first dose of pacritinib

7. Treatment with anticoagulation or antiplatelet agents, except for aspirin dosages of =100 mg per day, within the last 2 weeks

8. Treatment with a strong CYP3A4 inhibitor or a strong cytochrome P450 (CYP450) inducer within the last 2 weeks

9. Treatment with medications that can prolong the QTc interval within the last 2 weeks

10. Treatment with an experimental therapy within the last 28 days

11. 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)

12. 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.

13. New York Heart Association Class II, III, or IV congestive heart failure

14. 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.

15. 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)

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified