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Trial record 2 of 2 for:    PAC203

Phase 2 Study: 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

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ClinicalTrials.gov Identifier: NCT04884191
Recruitment Status : Completed
First Posted : May 12, 2021
Last Update Posted : May 12, 2021
Sponsor:
Information provided by (Responsible Party):
CTI BioPharma

Brief Summary:
This was an open-label, randomized, dose-finding study in patients with primary or secondary MF (Dynamic International Prognostic Scoring System [DIPSS] risk score of Intermediate-1 to High-Risk) who were previously treated with ruxolitinib. The study was designed to support a pacritinib dosage selection decision with evaluation of 3 dosages.

Condition or disease Intervention/treatment Phase
Primary Myelofibrosis Post-Polycythemia Vera Myelofibrosis Post- Essential Thrombocythemia Myelofibrosis Drug: Pacritinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 2 Study: 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
Actual Study Start Date : July 31, 2017
Actual Primary Completion Date : September 4, 2019
Actual Study Completion Date : September 4, 2019


Arm Intervention/treatment
Experimental: Pacritinib 100 mg QD Drug: Pacritinib
Pacritinib

Experimental: Pacritinib 100 mg BID Drug: Pacritinib
Pacritinib

Experimental: Pacritinib 200 mg BID Drug: Pacritinib
Pacritinib




Primary Outcome Measures :
  1. Spleen Volume Reduction Response (≥ 35%) [ Time Frame: From Baseline to Weeks 12 and 24 ]
    Number of patients achieving a ≥ 35% spleen volume reduction (SVR) as measured by magnetic resonance imaging (MRI, preferred) or computed tomography (CT) scans

  2. Spleen Volume [ Time Frame: From Baseline to Weeks 12 and 24 ]
    Percent change from baseline

  3. Total Symptom Score Analysis [ Time Frame: From Baseline to Weeks 12 and 24 ]
    Proportion of patients with ≥ 50% reduction in Total Symptom Score from baseline as assessed by the validated PRO instrument MPN-SAF TSS 2.0

  4. Patient Global Impression Assessment [ Time Frame: From Baseline to Weeks 12 and 24 ]
    Number of patients with improvement in PGIA


Secondary Outcome Measures :
  1. Spleen Length Reduction [ Time Frame: From Baseline to Weeks 24 ]
    Rate of reduction in spleen length from baseline

  2. Frequency of RBC's or platelet Transfusions [ Time Frame: At week 24 ]
    Number of patients

  3. Eastern Cooperative Oncology Group Performance Status [ Time Frame: At weeks 4, 12, 24, and 30 days post End-of-Treatment visit ]
  4. Safety: number of Adverse Events [ Time Frame: Randomization through 30 days post End-of-Treatment visit ]


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

Inclusion Criteria:

  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 with failure to benefit or intolerance as defined by at least one of the following:

    1. Treatment for ≥3 months with inadequate efficacy response defined as <10% SVR by MRI or <30% decrease from baseline in spleen length by physical examination or regrowth to these parameters following an initial response; and/or
    2. Treatment for ≥28 days complicated by either

    i. Development of a red blood cell (RBC) transfusion requirement (at least 2 units/month for 2 months) ii. National Cancer Institute (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 or patients with a single symptom score of ≥5 or 2 symptoms of ≥3, including only the symptoms of left upper quadrant pain, bone pain, itching, or night sweats
  6. Age ≥18 years old
  7. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  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 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 scan assessments during the study
  15. Able to understand and willing to complete symptom assessments using a PRO instrument
  16. Provision of 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. 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 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 (eg, surgery, trauma, or 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 based on the mean of triplicate ECGs or other factors that increase the risk for QT interval prolongation (eg, 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 treating physician, would limit compliance with study requirements
  20. Known seropositivity for human immunodeficiency virus
  21. Known active hepatitis A, B, or C virus infection
  22. Women who are pregnant or lactating
  23. 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): NCT04884191


Locations
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Sponsors and Collaborators
CTI BioPharma
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Responsible Party: CTI BioPharma
ClinicalTrials.gov Identifier: NCT04884191    
Other Study ID Numbers: PAC203
First Posted: May 12, 2021    Key Record Dates
Last Update Posted: May 12, 2021
Last Verified: May 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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