Pacritinib Versus Best Available Therapy to Treat Patients With Myelofibrosis and Thrombocytopenia

Phase 3

Terminated

• Conditions: Post-polycythemia Vera Myelofibrosis; Primary Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
• Interventions: Drug: Best Available Therapy; Drug: Pacritinib

• Registration Number: NCT02055781
• Lead Sponsor: CTI BioPharma

Brief Summary

Phase 3, randomized, controlled study to evaluate the safety and efficacy of oral pacritinib compared to Best Available Therapy (BAT) in patients with thrombocytopenia and primary or secondary myelofibrosis.

Detailed Description

Multicenter, randomized, controlled, phase 3 trial comparing the safety and efficacy of pacritinib with that of BAT in patients with thrombocytopenia and primary or secondary myelofibrosis. Approximately 300 eligible patients will be randomized in a 1:1:1 allocation to pacritinib 400 mg dosed QD, pacritinib 200 mg dosed BID, or BAT (includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry). Spleen volume will be measured by MRI or CT at baseline and every 12 weeks thereafter. An independent radiology facility (IRF), blind to treatment assignments, will measure spleen volumes. Patients will also be followed for safety, Leukemia Free Survival (LFS), Overall Survival (OS), frequency of red blood cell (RBC) and platelet transfusions, and other exploratory endpoints. An Independent Data Monitoring Committee (IDMC) will evaluate the safety of pacritinib.

Study Timeline

• Study Start: 2014-02
• Study First Submitted: 2014-02-03
• Study First Submitted QC: 2014-02-04
• Study First Posted: 2014-02-05
• Primary Completion: 2016-04
• Study Completion: 2016-04
• Results First Submitted: 2020-11-23
• Status Verified: 2021-10
• Results First Submitted QC: 2021-10-21
• Last Update Submitted: 2021-10-21
• Results First Posted: 2021-11-18
• Last Update Posted: 2021-11-18

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 311

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Best Available Therapy	Best Available Therapy	BAT includes any physician-selected treatment for myelofibrosis, such as approved JAK2 inhibitors administered according to package insert for patients with thrombocytopenia, and may include any treatment received before study entry.
Pacritinib, Once Daily	Pacritinib	Pacritinib 400 mg QD
Pacritinib, Twice Daily	Pacritinib	Pacritinib 200 mg BID

Primary Outcome Measures

Name	Time	Method
Spleen Volume Reduction	Baseline to Week 24	Proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline to week 24 as measured by magnetic resonance imaging (MRI) or computed tomography (CT).
Total Symptom Score (TSS) Reduction	Baseline to Week 24	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 (MPN-SAF TSS 2.0). Responses (on a scale from 0 \[absent\] to 10 \[worst imaginable\]) to questions about symptoms (tiredness, early satiety, abdominal discomfort, night sweats, pruritus, bone pain, and pain under the ribs on the left side) were used to calculate the TSS.

Trial Locations

Locations (122)

Mayo Clinic Arizona; 🇺🇸 Scottsdale, Arizona, United States

Arizona Clinical Research Center; 🇺🇸 Tucson, Arizona, United States

City of Hope; 🇺🇸 Duarte, California, United States

Moores Cancer Centre; 🇺🇸 La Jolla, California, United States

USC Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Stanford Cancer Center; 🇺🇸 Stanford, California, United States

Rocky Mountain Cancer Center; 🇺🇸 Boulder, Colorado, United States

George Washington University- Medical Faculty Associates; 🇺🇸 Washington, District of Columbia, United States

SCRI- Florida Cancer Specialists South Region; 🇺🇸 Fort Myers, Florida, United States

SCRI - Florida Cancer Specialists North Region; 🇺🇸 Saint Petersburg, Florida, United States

Scroll for more (112 remaining)