Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    PAC203
Previous Study | Return to List | Next Study

A Phase 2/3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis (PACIFICA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03165734
Recruitment Status : Recruiting
First Posted : May 24, 2017
Last Update Posted : January 28, 2020
Sponsor:
Collaborator:
The Physicians' Services Incorporated Foundation
Information provided by (Responsible Party):
CTI BioPharma

Brief Summary:

Phase 3 of this study is evaluating 200 mg BID of pacritinib compared to physician's choice (P/C) therapy in patients with MF and severe thrombocytopenia (platelet count <50,000/μL). Approximately 180 patients in total will be enrolled, randomized 2:1 to either pacritinib (approximately 120 patients) or to P/C therapy (approximately 60 patients)

Phase 2 was an open-label, randomized, dose-ranging study designed to identify the most appropriate dosage of pacritinib for future studies based on risk/benefit profile. Patients were randomized 1:1:1 to three dosage arms: 100mg QD, 100mg BID or 200mg BID. A total of 164 patients were randomized in the phase 2 portion of Study PAC203, and 161 (98.2%) patients received any treatment with pacritinib.

Condition or disease: Primary Myelofibrosis/Post-Polycythemia Vera Myelofibrosis/ Post-essential Thrombocythemia Myelofibrosis

Intervention/treatment: Drug-Pacritinib


Condition or disease Intervention/treatment Phase
Primary Myelofibrosis Post-polycythemia Vera Myelofibrosis Post-essential Thrombocythemia Myelofibrosis Drug: Pacritinib Drug: Physician's Choice medications Phase 2 Phase 3

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2/3 Study of Pacritinib An Open-Label, Randomized, Phase 2 Dose-Finding Study of Pacritinib in Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis Previously Treated With Ruxolitinib Phase 3 Study (PACIFICA):A Randomized, Controlled Phase 3 Study of Pacritinib Versus Physician's Choice in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis With Severe Thrombocytopenia (Platelet Count <50,000/μL)
Actual Study Start Date : June 26, 2017
Estimated Primary Completion Date : July 31, 2022
Estimated Study Completion Date : December 2, 2022


Arm Intervention/treatment
Active Comparator: Pacritinib 200 mg BID - Phase 3
2:1 to receive pacritinib 200 mg twice daily (BID) orally, at the same time of day, with or without food or the Physician's Choice (P/C) therapy (limited to single drugs from the following list: corticosteroids, hydroxyurea, thalidomide, lenalidomide, or low-dose ruxolitinib). The proposed P/C regimen for a patient must be selected prior to randomization.
Drug: Pacritinib
Oral administration. Supplied in capsules containing 100 mg (as the free base) in red cap/gray body size 0 opaque hard gelatin capsules. The inactive ingredients are microcrystalline cellulose, magnesium stearate, and polyethylene glycol 8000. Each capsule contains 146 mg of pacritinib citrate, which is equivalent to 100 mg pacritinib free base

Drug: Physician's Choice medications
Physician's Choice medications will be selected and administered according to the investigator's judgement. Investigators can select individual P/C agents but cannot combine agents or give them sequentially.
Other Names:
  • corticosteroids
  • hydroxyurea
  • lenalidomide
  • low-dose ruxolitinib
  • thalidomide

Experimental: Pacritinib 100 mg QD; 100 mg BID; 200 mg BID - Phase 2
1:1:1 to pacritinib 100 mg QD, pacritinib 100 mg BID, or pacritinib 200 mg BID orally, at the same time of day, with or without food
Drug: Pacritinib
Oral administration. Supplied in capsules containing 100 mg (as the free base) in red cap/gray body size 0 opaque hard gelatin capsules. The inactive ingredients are microcrystalline cellulose, magnesium stearate, and polyethylene glycol 8000. Each capsule contains 146 mg of pacritinib citrate, which is equivalent to 100 mg pacritinib free base




Primary Outcome Measures :
  1. Spleen volume [ Time Frame: From baseline to 24 weeks ]
    To compare the efficacy of pacritinib with that of physician's choice (P/C) therapy, as assessed by the proportion of patients achieving a ≥35% spleen volume reduction (SVR) as measured by magnetic resonance imaging (MRI, preferred) or computed tomography (CT) scans


Secondary Outcome Measures :
  1. Total Symptom Score (TSS) [ Time Frame: Between baseline and Week 24 ]
    To compare the efficacy of pacritinib with P/C therapy, as assessed by the proportion of patients achieving a ≥50% reduction in Total Symptom Score (TSS)

  2. Overall Survival (OS) [ Time Frame: until 2.5 years after the date of randomization ]
    To compare the overall survival (OS) of patients treated with pacritinib versus those treated with P/C

  3. Patient Global Impression of Change (PGIC) assessed at Week 24 [ Time Frame: End of Week 12 to 2 years following Week 24 visit ]
    To compare the percentage of patients who self-assess as "very much improved" or "much improved" as measured by the Patient Global Impression of Change (PGIC) in patients treated with pacritinib versus those treated with P/C


Other Outcome Measures:
  1. SVR of ≥35% [ Time Frame: Up to 24 Weeks ]
    Time to achievement of SVR of ≥35%

  2. Best response in SVR [ Time Frame: At 24 Weeks ]
    Best response in SVR by MRI or CT scan

  3. >25% SVR [ Time Frame: Between baseline and Week 24 ]
    Proportion of patients achieving >25% SVR

  4. Red blood cell (RBC) [ Time Frame: Baseline to End of Treatment ]
    Achievement of red blood cell (RBC) transfusion independence at Weeks 12 and 24

  5. hemoglobin level [ Time Frame: Weeks 12 and 24 ]
    Improvement in hemoglobin level without transfusion at Weeks 12 and 24

  6. platelet count [ Time Frame: Weeks 12 and 24 ]
    Improvement in platelet count at Weeks 12 and 24

  7. platelet transfusions [ Time Frame: Weeks 12 and 24 ]
    Frequency of platelet transfusions at Weeks 12 and 24

  8. PROMIS [ Time Frame: Baseline to Week 24 ]
    Improvement in fatigue as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) v.1.0 - Fatigue from Baseline through Week 24

  9. mutated allelic burden, gene expression, and pharmacodynamic (PD) biomarkers [ Time Frame: Baseline to up to 24 Weeks ]
    Changes in mutated allelic burden, gene expression, and pharmacodynamic (PD) biomarkers



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Phase 3 Diagnosis and Inclusion Criteria

  1. PMF, PPV-MF, or PET-MF
  2. Average platelet count of <50,000/µL at Screening (based on three measurements taken on different days; two measurements must be <50,000/µL, and none can be >60,000/µL)
  3. DIPSS Intermediate-1, Intermediate-2, or High risk (Passamonti et al 2010)
  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 or a single symptom score of ≥5 or two symptoms of ≥3, including only the symptoms of left upper quadrant pain, bone pain, itching, or night sweats
  6. Age ≥18 years
  7. Eastern Cooperative Oncology Group performance status 0 to 2
  8. Peripheral blast count of <10% throughout the Screening period and at baseline
  9. Absolute neutrophil count of ≥500/µL
  10. Left ventricular cardiac ejection fraction of ≥50% by echocardiogram or multigated acquisition (MUGA) scan
  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 defined by prothrombin time/international normalized ratio and partial thromboplastin time ≤1.5 × ULN
  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 scan assessments during the study
  15. Able to understand and willing to complete symptom assessments using a patient-reported outcome instrument
  16. Provision of signed informed consent

Exclusion Criteria

  1. Life expectancy <6 months
  2. Completed allogeneic stem cell transplant (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. Treatment with any MF-directed therapy within 14 days prior to treatment Day 1
  7. Any prior treatment with a JAK2 inhibitor for more than 90 days from the date of first administration. The 90-day JAK2 treatment period may overlap with the Screening period but may not extend to within 14 days prior to treatment Day 1.
  8. Prior treatment with more than one JAK2 inhibitor
  9. Treatment with an experimental therapy within 28 days prior to treatment Day 1
  10. Systemic treatment with a strong CYP3A4 inhibitor or a strong cytochrome P450 (CYP450) inducer within 14 days prior to treatment Day 1
  11. Significant recent bleeding history defined as National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade ≥2 within 3 months prior to treatment Day 1, unless precipitated by an inciting event (e.g., surgery, trauma, or injury)
  12. Systemic treatment with medications that increase the risk of bleeding, including anticoagulants, antiplatelet agents (except for aspirin dosages of ≤100 mg per day), anti-vascular endothelial growth factor (anti-vascular endothelial growth factor [VEGF]) agents, and daily use of COX-1 inhibiting nonsteroidal anti- inflammatory drugs (NSAIDs) within 14 days prior to treatment Day 1
  13. Systemic treatment with medications that can prolong the QT interval within 14 days prior to treatment Day 1
  14. Any history of CTCAE grade ≥2 non-dysrhythmia cardiac conditions within 6 months prior to treatment Day 1. Patients with asymptomatic grade 2 non- dysrhythmia cardiovascular conditions may be considered for inclusion, with the approval of the Medical Monitor, if stable and unlikely to affect patient safety.
  15. Any history of CTCAE grade ≥2 cardiac dysrhythmias within 6 months prior to treatment Day 1. 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.
  16. QT corrected by the Fridericia method (QTcF) 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], or history of long QT interval syndrome
  17. New York Heart Association Class II, III, or IV congestive heart failure
  18. Any active gastrointestinal or metabolic condition that could interfere with absorption of oral medication
  19. Active or uncontrolled inflammatory or chronic functional bowel disorder such as Crohn's Disease, inflammatory bowel disease, chronic diarrhea, or chronic constipation
  20. Other malignancy within 3 years prior to treatment Day 1, other than curatively treated basal cell or squamous cell skin or corneal cancer; curatively treated carcinoma in situ of the cervix; organ-confined prostate cancer with prostate-specific antigen (PSA) <20 ng/mL and National Comprehensive Cancer Network risk of Very Low, Low, or Favorable Intermediate; curatively treated non-metastatic prostate cancer with negative PSA; or in situ breast carcinoma after complete surgical resection
  21. 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
  22. Known seropositivity for human immunodeficiency virus
  23. Known active hepatitis A, B, or C virus infection
  24. Women who are pregnant or lactating
  25. Concurrent enrollment in another interventional trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03165734


Contacts
Layout table for location contacts
Contact: Sirin Artan Kahrs, MD 206-272-4386 sartankahrs@ctibiopharma.com

Locations
Show Show 74 study locations
Sponsors and Collaborators
CTI BioPharma
The Physicians' Services Incorporated Foundation

Layout table for additonal information
Responsible Party: CTI BioPharma
ClinicalTrials.gov Identifier: NCT03165734    
Other Study ID Numbers: PAC203
First Posted: May 24, 2017    Key Record Dates
Last Update Posted: January 28, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by CTI BioPharma:
myelofibrosis
pacritinib
Post-polycythemia Vera Myelofibrosis
Post-essential Thrombocythemia Myelofibrosis
Ruxolitinib
Bone Marrow Disease
Hematologic Diseases
Blood Platelet Disorders
Hemorrhagic Disorders
Splenomegaly
Anemia
Spleen volume
Spleen
Additional relevant MeSH terms:
Layout table for MeSH terms
Polycythemia Vera
Primary Myelofibrosis
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders
Thalidomide
Lenalidomide
Hydroxyurea
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antisickling Agents