Oral Pacritinib Versus Best Available Therapy to Treat Myelofibrosis With Thrombocytopenia - Full Text View

Purpose

The primary hypothesis of the study is that treatment with either once-daily or twice-daily pacritinib results in a greater proportion of patients with thrombocytopenia and myelofibrosis achieving ≥ 35% reduction in spleen volume from baseline to Week 24 than treatment with Best Available Therapy, and a greater proportion of patients achieving a ≥ 50% reduction in total symptom score from baseline to Week 24 as measured by the Myeloproliferative Neoplasm Symptom Assessment Form 2.0.

Condition	Intervention	Phase
Primary Myelofibrosis Post-polycythemia Vera Myelofibrosis Post-essential Thrombocythemia Myelofibrosis	Drug: Pacritinib Drug: Best Available Therapy	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Randomized Controlled Phase 3 Study of Oral Pacritinib Versus Best Available Therapy in Patients With Thrombocytopenia and Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis

Resource links provided by NLM:

Genetics Home Reference related topics: essential thrombocythemia polycythemia vera primary myelofibrosis

Genetic and Rare Diseases Information Center resources: Essential Thrombocythemia Myelofibrosis Chronic Myeloproliferative Disorders Splenomegaly Polycythemia Vera

U.S. FDA Resources

Further study details as provided by CTI BioPharma:

Primary Outcome Measures:

Efficacy [ Time Frame: Baseline to Week 24 ]
To compare the efficacy of two dose-schedule arms of pacritinib (pooled once-daily and twice-daily dosing arms) with that of Best Available Therapy in patients with thrombocytopenia and primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis; the efficacy measure for this analysis is the proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to week 24 by magnetic resonance imaging (MRI) or computed tomography (CT) and the proportion of patients achieving a ≥ 50% reduction in total symptom score from baseline to Week 24 as measured by the Myeloproliferative Neoplasm Symptom Assessment Form 2.0.

Secondary Outcome Measures:

Efficacy [ Time Frame: Baseline to Week 24 ]
To compare the efficacy of once-daily pacritinib with that of Best Available Therapy, as assessed by the proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to Week 24 by magnetic resonance imaging (MRI) or computed tomography (CT) and the proportion of patients achieving a ≥ 50% reduction in the total symptom score from baseline to Week 24 on the Myeloproliferative Neoplasm Symptom Assessment Form 2.0.
Efficacy [ Time Frame: Baseline to Week 24 ]
To compare the efficacy of twice-daily pacritinib with that of Best Available Therapy, as assessed by the proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to Week 24 by magnetic resonance imaging (MRI) or computed tomography (CT) and the proportion of patients achieving a ≥ 50% reduction in the total symptom score from baseline to Week 24 on the myeloproliferate Neoplasm Symptom Assessment Form 2.0.


Estimated Enrollment:	300
Study Start Date:	December 2013
Study Completion Date:	November 2016
Primary Completion Date:	August 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Pacritinib, Once Daily Pacritinib 400 mg taken orally, once daily	Drug: Pacritinib
Experimental: Pacritinib, Twice Daily Pacritinib 200 mg taken orally, twice daily	Drug: Pacritinib
Active Comparator: Best Available Therapy Best Available Therapy includes any physician-selected treatment for primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis, such as approved JAK2 inhibitors, and may include any treatment received before study entry. Best Available Therapy may include ruxolitinib, other approved JAK2 inhibitors, hydroxyurea, glucocorticoids, erythropoietic agents, immunomodulatory agents, mercaptopurine, danazol, interferons, cytarabine, melphalan, or other agents and may also include no treatment and symptom-directed treatment without myelofibrosis-specific treatment.	Drug: Best Available Therapy

Eligibility


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

Criteria

Inclusion Criteria:

Intermediate -1 or -2 or high-risk Myelofibrosis (per Passamonti et al 2010)
Thrombocytopenia (platelet count ≤ 100,000/µL) at any time after signing informed consent
Palpable splenomegaly ≥ 5 cm on physical examination
Total Symptom Score ≥ 13 on the MPN-SAF TSS 2.0, not including the inactivity question
Patients who are platelet or red blood cell transfusion-dependent are eligible
Adequate white blood cell counts (with low blast counts), liver function, and renal function
At least 6 months from prior splenic irradiation
At least 1-4 weeks since prior myelofibrosis therapy, including any erythropoietic or thrombopoietic agent
Not pregnant, not lactating, and agree to use effective birth control
Able and willing to undergo frequent MRI or CT assessments and complete symptom assessments using a patient-reported outcome instrument

Exclusion Criteria:

Prior treatment with more than 2 JAK2 inhibitors or with pacritinib
There is no maximum cumulative prior JAK2 inhibitor treatment
History of (or plans to undergo) spleen removal surgery or allogeneic stem cell transplant
Ongoing gastrointestinal medical condition such as Crohn's disease, Inflammatory bowel disease, chronic diarrhea, or constipation
Active bleeding that requires hospitalization during the screening period
Cardiovascular disease, including recent history or currently clinically symptomatic and uncontrolled: congestive heart failure, arrhythmia, angina, QTc prolongation or other QTc risk factors, myocardial infarction
Other malignancy within last 3 years other than certain limited skin, cervical, prostate, breast, or bladder cancers
Other ongoing, uncontrolled illnesses (including HIV infection and active hepatitis A, B, or C), psychiatric disorder, or social situation that would prevent good care on this study
Life expectancy < 6 months

Contacts and Locations

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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02055781

Show 122 Study Locations

Sponsors and Collaborators

CTI BioPharma

Investigators


Study Director:	Mary Campbell, MD	CTI BioPharma

More Information


Responsible Party:	CTI BioPharma
ClinicalTrials.gov Identifier:	NCT02055781 History of Changes
Other Study ID Numbers:	PERSIST-2 (PAC326)
Study First Received:	February 3, 2014
Last Updated:	December 15, 2016

Keywords provided by CTI BioPharma:


Myelofibrosis Post-Polycythemia Vera Myelofibrosis Post-Essential Thrombocythemia Myelofibrosis Primary Myelofibrosis Polycythemia Polycythemia Vera Thrombocythemia, Essential Thrombocythemia Myeloproliferative Disorders Bone Marrow Disease Hematologic Diseases Blood Platelet Disorders	Hemorrhagic Disorders Splenomegaly Pacritinib MPN-SAF MPN-SAF TSS Anemia Myeloproliferative Myeloproliferative Neoplasm Spleen Spleen volume Thrombocytopenia SB1518

Additional relevant MeSH terms:


Primary Myelofibrosis Thrombocytopenia Polycythemia Polycythemia Vera Thrombocytosis Thrombocythemia, Essential	Myeloproliferative Disorders Bone Marrow Diseases Hematologic Diseases Blood Platelet Disorders Blood Coagulation Disorders Hemorrhagic Disorders

ClinicalTrials.gov processed this record on July 17, 2017

Oral Pacritinib Versus Best Available Therapy to Treat Myelofibrosis With Thrombocytopenia (PAC326)