Clinical Trial Details

NCT ID: NCT03165734
Date Last Changed: October 10, 2017

Overview

Research Study Summary

A Phase 2 clinical study for patients with Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis

Research Study Title

Open-Label, Randomized, Phase2 Dose-Finding Study of Pacritinib in Patients With Thrombocytopenia and Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis Previously Treated With Ruxolitinib

Purpose

This is a Bayesian adaptive dose-finding study in patients with primary or secondary myelofibrosis:

  1. who have failed therapy with ruxolitinib on the basis of intolerance or loss of efficacy,

  2. are thrombocytopenic (platelet count of ≤100,000/μL),

  3. highly symptomatic (DIPSS risk score of Intermediate-1 to High Risk),

  4. and have splenomegaly (assessed by physical examination).

The study is designed to support a pacritinib dosage selection decision. Three dosages will be evaluated, with patients randomized 1:1:1 to pacritinib 100 mg quaque die (QD), pacritinib 100 mg bis in die (BID), or pacritinib 200 mg bis in die (BID). Assigned treatment will continue for 24 weeks unless the patient experiences progressive disease, intolerable AEs, withdraws consent, or until the assigned treatment arm is closed. All patients should complete all visit procedures through Week 24, including patients who stop pacritinib treatment or have protocol-defined progressive disease prior to Week 24, unless patient withdraws consent, dies, undergoes splenic irradiation or splenectomy, or initiates any nonprotocol-directed anti-myelofibrosis treatment. The dosage selection process will be based on pre-specified efficacy and safety parameters, including model-based dose-response. The maximum duration of trial participation for an individual patient will be approximately 7 months. The estimated duration of the entire study is approximately 2 years if the maximum number of patients are enrolled.

To Learn more

Recruitment Details

Phase
2
Gender
All
Age
18 and up
Overall Status
Recruiting
Lead Sponsor
CTI BioPharma
Duration
18 Months
Facility Type
N/A
Compensation

Eligibility

All ages 18 Years and up

Inclusion Criteria:

  1. Primary myelofibrosis, post-polycythemia vera myelofibrosis, or Post-essential thrombocythemia myelofibrosis

  2. Dynamic International Prognostic Scoring System (DIPSS) Intermediate-1, Intermediate -2, or High risk (Passamonti et al 2010)

  3. Prior ruxolitinib treatment failure or intolerance as defined by:

  4. Treatment for ≥6 months with inadequate efficacy response (any measure) in the judgement of the investigator

  5. Treatment for ≥28 days complicated by either:

i. Red Blood Cell transfusion ii. National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 AEs of thrombocytopenia, anemia, hematoma, and/or hemorrhage while being treated with a dosage of < 20 mg BID

  1. Palpable splenomegaly ≥5 cm below the lower costal margin (LCM) in the midclavicular line as assessed by physical examination

  2. 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

  3. Total Symptom Score (TSS) of ≥10 on the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS 2.0)

  4. Age ≥18 years old

  5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

  6. Peripheral blast count of < 10%

  7. Absolute neutrophil count of > 500/μL

  8. Adequate liver and renal function, defined by liver transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase and alanine aminotransferase/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

  9. Adequate coagulation function, defined by prothrombin time PT)/international normalized ratio (INR), partial thromboplastin time (PTT), or thrombin time (TT) of ≤1.5 × ULN

  10. Left ventricular cardiac ejection fraction of ≥45% by echocardiogram or multigated acquisition (MUGA) scan

  11. QTc interval of < 450 ms as assessed by ECG and corrected by the Fridericia method

  12. If fertile, willing to use effective birth control methods during the study

  13. Willing to undergo and able to tolerate frequent MRI or CT assessments during the study

  14. Able to understand and willing to complete symptom assessments using a patient-reported outcomes instrument

  15. Provision of informed consent

Exclusion Criteria:

  1. Life expectancy < 6 months

  2. Completed allogeneic stem cell transplantation (ASCT) or are eligible for and willing to complete Completed allogeneic stem cell transplantation (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 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) grade ≥2 within the last 3 months, unless precipitated by an inciting event (e.g., surgery, trauma, injury)

  10. Any history of Common Terminology Criteria for Adverse Events (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 Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2 cardiac dysrhythmias within the last 6 months. Patients with non-QTc Common Terminology Criteria for Adverse Events (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(milliequivalent)/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

Site Locations (12)

Country State City Zip Facility and Contact
United States California Duarte 91010 City of Hope
United States California Stanford 94305 Stanford Cancer Center, Palo Alto
United States District of Columbia Washington, D.C. 20037 George Washington University-Medical Faculty Associates
United States Florida Fort Myers 33901 Florida Cancer Specialists & Research Institute
United States Florida Saint Petersburg 33705 Florida Cancer Specialists
United States Florida West Palm Beach 33401 Florida Cancer Specialists
United States Illinois Chicago 60637 The University of Chicago Medical Center
United States Maryland Baltimore 21229 Saint Agnes Hospital
United States Missouri Saint Louis 63110 Washington University School of Medicine-Siteman Cancer Center
United States New York New York 10029 Icahn School of Medicine at Mount Sinai
United States Tennessee Nashville 37203 The Sarah Cannon Research Institute-Tennessee Oncology
United States Washington Seattle 98109 Fred Hutchinson Cancer Research Center

Contact

Debra Jones
206-282-7100
E-mail:

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