Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000740695
Ethics application status
Approved
Date submitted
3/07/2014
Date registered
11/07/2014
Date last updated
11/07/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
Oral Pacritinib Versus Best Available Therapy to Treat Myelofibrosis With Thrombocytopenia (PAC326)
Scientific 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
Secondary ID [1] 284352 0
NCT02055781
Universal Trial Number (UTN)
Trial acronym
Persist-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Myelofibrosis
 291507 0
Condition category
Condition code
Cancer 291877 291877 0 0
Myeloma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pacritinib (oral) 400mg QD or BID daily for 24 weeks, PK (Pharmocokinetic)/PD (Pharmacodynamic) analysis and drug tablet return
Intervention code [1] 289077 0
Treatment: Drugs
Comparator / control treatment
BAT (Best Available Treatment) varies from site to site cant be described as very different for each patient/treatment/site
Control group
Active

Outcomes
Primary outcome [1] 291796 0
Efficacy [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 greater than 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 greater than 50% reduction in total symptom score from baseline to Week 24 as measured by the Myeloproliferative Neoplasm Symptom Assessment Form 2.0.
Timepoint [1] 291796 0
Baseline to Week 24
Secondary outcome [1] 307565 0
Efficacy [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 greater than 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 greater than 50% reduction in the total symptom score from baseline to Week 24 on the Myeloproliferative Neoplasm Symptom Assessment Form 2.0.
Timepoint [1] 307565 0
Baseline to Week 24
Secondary outcome [2] 307566 0
Efficacy [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 greater than 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 greater than 50% reduction in the total symptom score from baseline to Week 24 on the myeloproliferate Neoplasm Symptom Assessment Form 2.0.
Timepoint [2] 307566 0
Baseline to Week 24

Eligibility
Key inclusion criteria
Intermediate -1 or -2 or high-risk Myelofibrosis (per Passamonti et al 2010)
Thrombocytopenia (platelet count greater than 100,000/microlitre) at any time after signing informed consent
Palpable splenomegaly greater than 5 cm on physical examination
Total Symptom Score less than 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Prior treatment with more than 2 JAK2 inhibitors or with pacritinib
More than 6 months of 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Active Comparator: Best Available Therapy versus two doses of Pacritinib which will be randomised in a 1:1:1 ratio. Open Trial allocation not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/07/2014
Actual
4/07/2014
Date of last participant enrolment
Anticipated
30/06/2015
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA,VIC
Recruitment outside Australia
Country [1] 5935 0
New Zealand
State/province [1] 5935 0
Country [2] 5936 0
United States of America
State/province [2] 5936 0
Country [3] 5937 0
France
State/province [3] 5937 0
Country [4] 5938 0
United Kingdom
State/province [4] 5938 0
Country [5] 5939 0
Spain
State/province [5] 5939 0
Country [6] 6193 0
Hungary
State/province [6] 6193 0

Funding & Sponsors
Funding source category [1] 288986 0
Commercial sector/Industry
Name [1] 288986 0
Cell Therapeutics Inc.
Country [1] 288986 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Cell Therapeutics Inc.
Address
3101 Western Avenue, Suite 600
Seattle, WA 98121
Country
United States of America
Secondary sponsor category [1] 287666 0
None
Name [1] 287666 0
Address [1] 287666 0
Country [1] 287666 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290797 0
Bellberry Limited
Ethics committee address [1] 290797 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 290797 0
Australia
Date submitted for ethics approval [1] 290797 0
26/03/2014
Approval date [1] 290797 0
20/06/2014
Ethics approval number [1] 290797 0
2014-03-120

Summary
Brief summary
This study will compare the chemotherapy drug, Pacritinib, against the best available treatment for Thrombocytopenia and Myelofibrosis. You may be eligible to join this study if you aged 18 years or above and have been diagnosed with thrombocytopenia and/or myelofibrosis. Participants in this study are randomly allocated (by chance) to one of three groups. Participants in the first group will receive one dose of 400mg of oral Pacritinib for 24 weeks or until progression has occurred. Participants in the second group will receive two doses of 200mg of oral Pacritinib daily for up to 24 weeks or until progression occurs. Participants in the third group will receive best available treatment - which will be chosen by your treating physician. Participants will undergo magnetic resonance imaging (MRI) or computed tomography (CT) scans to determine spleen volume and will be assessed for total symptom score using the Myeloproliferative Neoplasm Symptom Assessment Form 2.0. These assessments will occur 12 weekly. Patients may crossover from the BAT (Best available treatment) arm to Pacritinib at the discretion of the Investigator.
Trial website
http://www.celltherapeutics.com/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 47322 0
Dr Andrew Perkins
Address 47322 0
Icon Cancer Care
PO Box 1879
MILTON QLD 4064
Country 47322 0
Australia
Phone 47322 0
+61 07 3737 4883
Fax 47322 0
+61 07 3737 4873
Email 47322 0
[email protected]
Contact person for public queries
Name 47323 0
Mr Vince Holmes
Address 47323 0
Ockham Oncology
The Logan Building, Roslin Biocentre, Edinburgh, EH25 9TT United Kingdom
Country 47323 0
United Kingdom
Phone 47323 0
+44 (0)238.032.1226
Fax 47323 0
Email 47323 0
[email protected]
Contact person for scientific queries
Name 47324 0
Dr Valentina Zhukova-Harrill, MD
Address 47324 0
Ockham Oncology
8000 Regency Parkway, Suite 360, Cary, NC 27518 United States
Country 47324 0
United States of America
Phone 47324 0
+1 919 462 7566
Fax 47324 0
Email 47324 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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