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Trial record 7 of 22 for:    pacritinib

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

This study is currently recruiting participants.
Verified October 2017 by CTI BioPharma
Sponsor:
ClinicalTrials.gov Identifier:
NCT03165734
First Posted: May 24, 2017
Last Update Posted: November 22, 2017
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.
Collaborator:
Covance
Information provided by (Responsible Party):
CTI BioPharma
  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.


Condition Intervention Phase
Primary Myelofibrosis Post-polycythemia Vera Myelofibrosis Post-essential Thrombocythemia Myelofibrosis Drug: Pacritinib Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by CTI BioPharma:

Primary Outcome Measures:
  • Spleen volume [ Time Frame: 24 weeks ]
    The primary efficacy variable for dosage selection is the percent reduction in spleen volume from baseline as measured by MRI or CT. For evaluation as part of the dose-response relationship will include the percentage of patients who achieve at least 35% reduction in spleen volume


Secondary Outcome Measures:
  • Percentage of patients with CTCAE grade ≥3 cardiac AEs, CTCAE grade ≥3 hemorrhage AEs, CTCAE grade ≥4 thrombocytopenia toxicity, or CTCAE grade ≥4 anemia toxicity [ Time Frame: Day 0 through the patient's last day of study participation, approximately 8 months ]
    The safety population is defined as all randomized patients who received at least one dose of study treatment. For screened patients who are not randomized, only SAEs occurring between the time of informed consent and determination of screen failure are to be reported.


Estimated Enrollment: 105
Actual Study Start Date: June 26, 2017
Estimated Study Completion Date: March 1, 2019
Estimated Primary Completion Date: December 1, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pacritinib 100 mg QD
Pacritinib 100 mg (1 capsule) QD 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 capsules contains 146 mg of pacritinib citrate, which is equivalent to 100 mg pacritinib free base
Experimental: Pacritinib 100 mg BID
Pacritinib 100 mg (1 capsule) 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 capsules contains 146 mg of pacritinib citrate, which is equivalent to 100 mg pacritinib free base
Experimental: Pacritinib 200 mg BID
Pacritinib 200 mg (2 capsules) 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 capsules contains 146 mg of pacritinib citrate, which is equivalent to 100 mg pacritinib free base

Detailed Description:

The Sponsor will collect PK samples from all patients in each dosing arm at the end of Week 12 and Week 24 at the following timepoints: 0 hours (predose), 4 hours postdose (±10 minutes), and 8 hours postdose (±15 minutes). In addition, PD samples will be collected on Day 1 (Baseline), Week 12, and Week 24 at 0 hours (predose).

This study will utilize planned frequent monitoring by an Independent Data Monitoring Committee (IDMC). The first IDMC meeting will occur once 30 patients have been randomized and will meet approximately quarterly thereafter. To minimize the patient exposure to minimally effective dosages, an interim analysis of the primary efficacy and safety data will be performed to allow an earlier decision to discontinue an arm that is unlikely to achieve at least 10% SVR at Week 24. The interim analysis occurs when 15 patients from each arm have completed Week 12 evaluations and have evaluable spleen volume data by MRI or CT. IDMC will review efficacy and safety data, including interim analysis, and make recommendations on:

  1. Closing treatment arm(s) and expanding enrollment in remaining treatment arm(s)
  2. Pausing enrollment due to cardiac or hemorrhage adverse events
  3. Dosage for further clinical studies
  Eligibility

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.


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

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:

    1. Treatment for ≥6 months with inadequate efficacy response (any measure) in the judgement of the investigator
    2. 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

  4. Palpable splenomegaly ≥5 cm below the lower costal margin (LCM) in the midclavicular line as assessed by physical examination
  5. 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
  6. Total Symptom Score (TSS) of ≥10 on the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS 2.0)
  7. Age ≥18 years old
  8. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
  9. Peripheral blast count of <10%
  10. Absolute neutrophil count of >500/μL
  11. 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
  12. Adequate coagulation function, defined by prothrombin time PT)/international normalized ratio (INR), partial thromboplastin time (PTT), or thrombin time (TT) of ≤1.5 × ULN
  13. Left ventricular cardiac ejection fraction of ≥45% by echocardiogram or multigated acquisition (MUGA) scan
  14. QTc interval of <450 ms as assessed by ECG and corrected by the Fridericia method
  15. If fertile, willing to use effective birth control methods during the study
  16. Willing to undergo and able to tolerate frequent MRI or CT assessments during the study
  17. Able to understand and willing to complete symptom assessments using a patient-reported outcomes instrument
  18. 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
  Contacts and Locations
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
Contact: Debra Jones 206-282-7100 djones@ctibiopharma.com
Contact: Monica Gelder 206-282-7100 mgelder@ctibiopharma.com

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
UCLA Jonsson Comprehensive Cancer Center Recruiting
Los Angeles, California, United States, 90095
Stanford Cancer Center, Palo Alto Recruiting
Stanford, California, United States, 94305
United States, District of Columbia
George Washington University-Medical Faculty Associates Recruiting
Washington, District of Columbia, United States, 20037
United States, Florida
Florida Cancer Specialists & Research Institute Recruiting
Fort Myers, Florida, United States, 33901
Florida Cancer Specialists Recruiting
Saint Petersburg, Florida, United States, 33705
Florida Cancer Specialists Recruiting
West Palm Beach, Florida, United States, 33401
United States, Illinois
The University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637
United States, Kansas
University of Kansas Cancer Center and Medical Pavilion Recruiting
Westwood, Kansas, United States, 66205
United States, Maryland
Saint Agnes Hospital Recruiting
Baltimore, Maryland, United States, 21229
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Missouri
Washington University School of Medicine-Siteman Cancer Center Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Icahn School of Medicine at Mount Sinai Recruiting
New York, New York, United States, 10029
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44106
United States, Tennessee
The Sarah Cannon Research Institute-Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States, 98109
Sponsors and Collaborators
CTI BioPharma
Covance
  More Information

Responsible Party: CTI BioPharma
ClinicalTrials.gov Identifier: NCT03165734     History of Changes
Other Study ID Numbers: PAC203
First Submitted: May 17, 2017
First Posted: May 24, 2017
Last Update Posted: November 22, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by CTI BioPharma:
pacritinib
myelofibrosis
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:
Primary Myelofibrosis
Thrombocytopenia
Polycythemia
Polycythemia Vera
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Blood Platelet Disorders
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Blood Coagulation Disorders
Hemorrhagic Disorders