Pacritinib Versus Best Available Therapy to Treat Myelofibrosis

Sponsor
CTI BioPharma (Industry)
Overall Status
Terminated
CT.gov ID
NCT01773187
Collaborator
(none)
327
81
2
39
4
0.1

Study Details

Study Description

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 primary or secondary myelofibrosis.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

Multicenter, randomized, controlled, phase 3 trial comparing the safety and efficacy of pacritinib with that of BAT in patients with primary or secondary myelofibrosis. Approximately 322 eligible patients will be randomized in a 2:1 allocation to pacritinib (400mg QD) or BAT (includes any physician-selected treatment for myelofibrosis with the exclusion of JAK inhibitors (inhibitors of Janus kinases)). 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 Design

Study Type:
Interventional
Actual Enrollment :
327 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Controlled Phase 3 Study of Oral Pacritinib Versus Best Available Therapy in Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis
Actual Study Start Date :
Jan 1, 2013
Actual Primary Completion Date :
Jan 1, 2015
Actual Study Completion Date :
Apr 1, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pacritinib

Pacritinib 400 mg QD

Drug: Pacritinib

Active Comparator: Best Available Therapy

BAT includes any physician-selected treatment for primary or secondary myelofibrosis with the exclusion of JAK inhibitors (inhibitors of Janus kinases)

Drug: Best Available Therapy

Outcome Measures

Primary Outcome Measures

  1. Spleen Volume Reduction [Baseline to Week 24]

    Number 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)

Secondary Outcome Measures

  1. Total Symptom Score (TSS) Reduction [Baseline to Week 24]

    Number of patients with >= 50% reduction in total 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Intermediate -1 or -2 or high-risk Myelofibrosis (per Passamonti et al 2010)

  • 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

  • No spleen radiation therapy for 6-12 months

  • Last therapy for myelofibrosis was 2-4 weeks ago, including any erythropoietic or thrombopoietic agent

  • Not pregnant, not lactating, and agree to use effective birth control

Exclusion Criteria:
  • Prior treatment with a JAK2 inhibitor

  • 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

  • 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

Locations

Site City State Country Postal Code
1 CTI Investigational Site 10002 Scottsdale Arizona United States 85259
2 CTI Investigational Site 10004 Omaha Nebraska United States 68198
3 CTI Investigational Site 10001 Morristown New Jersey United States 07962
4 CTI Investigational Site 10003 Greenville South Carolina United States 29601
5 CTI Investigational Site 61006 Box Hill Australia
6 CTI Investigational Site 61001 Coffs Harbour Australia
7 CTI Investigational Site 61005 Geelong Australia
8 CTI Investigational Site 61003 Gosford Australia
9 CTI Investigational Site 61004 Hobart Australia
10 CTI Investigational Site 61002 Milton Australia
11 CTI Investigational Site 32002 Antwerp Belgium
12 CTI Investigational Site 32003 Antwerp Belgium
13 CTI Investigational Site 32001 Brugge Belgium
14 CTI Investigational Site 32005 Bruxelles Belgium
15 CTI Investigational Site 32004 La Louviere Belgium
16 CTI Investigational Site 42003 Brno Czechia
17 CTI Investigational Site 42001 Olomouc Czechia
18 CTI Investigational Site 42002 Plzen Czechia
19 CTI Investigational Site 42004 Prague Czechia
20 CTI Investigational Site 33005 Amiens France
21 CTI Investigational Site 33006 Caen France
22 CTI Investigational Site 33011 Grenoble France
23 CTI Investigational Site 33012 Lens France
24 CTI Investigational Site 33007 Lille France
25 CTI Investigational Site 33001 Nimes Cedex France
26 CTI Investigational Site 33004 Paris France
27 CTI Investigational Site 33008 Paris France
28 CTI Investigational Site 33009 Pessac France
29 CTI Investigational Site 33010 Pierre Benite France
30 CTI Investigational Site 33003 Strasbourg France
31 CTI Investigational Site 33002 Toulouse France
32 CTI Investigational Site 49006 Berlin Germany
33 CTI Investigational Site 49007 Berlin Germany
34 CTI Investigational Site 49003 Dresden Germany
35 CTI Investigational Site 49008 Essen Germany
36 CTI Investigational Site 49002 Freiburg Germany
37 CTI Investigational Site 49001 Koln Germany
38 CTI Investigational Site 49005 Mainz Germany
39 CTI Investigational Site 49004 Munchen Germany
40 CTI Investigational Site 49009 Munster Germany
41 CTI Investigational Site 36002 Budapest Hungary
42 CTI Investigational Site 36005 Debrecen Hungary
43 CTI Investigational Site 36006 Gyula Hungary
44 CTI Investigational Site 36003 Kaposvar Hungary
45 CTI Investigational Site 36004 Kecskemet Hungary
46 CTI Investigational Site 36001 Szeged Hungary
47 CTI Investigational Site 36008 Szolnok Hungary
48 CTI Investigational Site 36007 Szombathely Hungary
49 CTI Investigational Site 39003 Bologna Italy
50 CTI Investigational Site 39001 Firenze Italy
51 CTI Investigational Site 39005 Milano Italy
52 CTI Investigational Site 39004 Monza Italy
53 CTI Investigational Site 39002 Padova Italy
54 CTI Investigational Site 39008 Reggio Emilia Italy
55 CTI Investigational Site 39006 Rimini Italy
56 CTI Investigational Site 31001 Amsterdam Netherlands
57 CTI Investigational Site 31002 Maastricht Netherlands
58 CTI Investigational Site 31003 Rotterdam Netherlands
59 CTI Investigational Site 31004 Utrecht Netherlands
60 CTI Investigational Site 64001 Christchurch New Zealand
61 CTI Investigational Site 64004 Dunedin New Zealand
62 CTI Investigational Site 64002 Hamilton New Zealand
63 CTI Investigational Site 64003 Takapuna New Zealand
64 CTI Investigational Site 70011 Izhevsk Russian Federation
65 CTI Investigational Site 70008 Moscow Russian Federation
66 CTI Investigational Site 70009 Moscow Russian Federation
67 CTI Investigational Site 70002 Petrozavodsk Russian Federation
68 CTI Investigational Site 70010 Saint Petersburg Russian Federation
69 CTI Investigational Site 70005 Samara Russian Federation
70 CTI Investigational Site 70006 Sochi Russian Federation
71 CTI Investigational Site 70001 St. Petersburg Russian Federation
72 CTI Investigational Site 70004 St. Petersburg Russian Federation
73 CTI Investigational Site 70007 Volgograd Russian Federation
74 CTI Investigational Site 44004 Birmingham United Kingdom
75 CTI Investigational Site 44008 Bournemouth United Kingdom
76 CTI Investigational Site 44002 Cambridge United Kingdom
77 CTI Investigational Site 44003 Cardiff United Kingdom
78 CTI Investigational Site 44001 London United Kingdom
79 CTI Investigational Site 44007 London United Kingdom
80 CTI Investigational Site 44006 Manchester United Kingdom
81 CTI Investigational Site 44005 Oxford United Kingdom

Sponsors and Collaborators

  • CTI BioPharma

Investigators

  • Study Director: Beth Ziemba, VP, Pharmacovigilance, Clinical Operations, QA

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:
CTI BioPharma
ClinicalTrials.gov Identifier:
NCT01773187
Other Study ID Numbers:
  • PERSIST-1 (PAC325)
First Posted:
Jan 23, 2013
Last Update Posted:
Sep 29, 2020
Last Verified:
Sep 1, 2020

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Pacritinib Best Available Therapy
Arm/Group Description Pacritinib 400 mg QD BAT includes any physician-selected treatment for primary or secondary myelofibrosis with the exclusion of JAK inhibitors (inhibitors of Janus kinases).
Period Title: Overall Study
STARTED 220 107
COMPLETED 167 75
NOT COMPLETED 53 32

Baseline Characteristics

Arm/Group Title Pacritinib Best Available Therapy Total
Arm/Group Description Pacritinib 400 mg QD BAT includes any physician-selected treatment for primary or secondary myelofibrosis with the exclusion of JAK inhibitors (inhibitors of Janus kinases). Total of all reporting groups
Overall Participants 220 107 327
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
Between 18 and 65 years
85
38.6%
52
48.6%
137
41.9%
>=65 years
135
61.4%
55
51.4%
190
58.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
65.5
(10.85)
64.8
(9.12)
65.3
(10.31)
Sex: Female, Male (Count of Participants)
Female
95
43.2%
47
43.9%
142
43.4%
Male
125
56.8%
60
56.1%
185
56.6%
Region of Enrollment (participants) [Number]
New Zealand
16
7.3%
4
3.7%
20
6.1%
Netherlands
13
5.9%
8
7.5%
21
6.4%
Belgium
8
3.6%
1
0.9%
9
2.8%
Hungary
49
22.3%
21
19.6%
70
21.4%
Czechia
9
4.1%
9
8.4%
18
5.5%
United States
3
1.4%
2
1.9%
5
1.5%
Italy
11
5%
10
9.3%
21
6.4%
United Kingdom
19
8.6%
6
5.6%
25
7.6%
Australia
29
13.2%
17
15.9%
46
14.1%
France
26
11.8%
9
8.4%
35
10.7%
Germany
2
0.9%
2
1.9%
4
1.2%
Russia
35
15.9%
18
16.8%
53
16.2%

Outcome Measures

1. Primary Outcome
Title Spleen Volume Reduction
Description Number 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)
Time Frame Baseline to Week 24

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Pacritinib Best Available Therapy
Arm/Group Description Pacritinib 400 mg QD BAT includes any physician-selected treatment for primary or secondary myelofibrosis with the exclusion of JAK inhibitors (inhibitors of Janus kinases).
Measure Participants 220 107
Count of Participants [Participants]
42
19.1%
5
4.7%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pacritinib, Best Available Therapy
Comments Pre-specified
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.0003
Comments
Method Fisher Exact
Comments
2. Secondary Outcome
Title Total Symptom Score (TSS) Reduction
Description Number of patients with >= 50% reduction in total 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.
Time Frame Baseline to Week 24

Outcome Measure Data

Analysis Population Description
The original version (MPN-SAF TSS) was administered to the first 179 subjects enrolled in the study. The subsequent 148 enrolled subjects were administered the MPN-SAF TSS 2.0 and comprise the ITT population for this endpoint.
Arm/Group Title Pacritinib Best Available Therapy
Arm/Group Description Pacritinib 400 mg QD BAT includes any physician-selected treatment for primary or secondary myelofibrosis with the exclusion of JAK inhibitors (inhibitors of Janus kinases).
Measure Participants 100 48
Count of Participants [Participants]
19
8.6%
5
4.7%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Pacritinib, Best Available Therapy
Comments Pre-specified
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.2368
Comments
Method Fisher Exact
Comments

Adverse Events

Time Frame Time of signing informed consent through 30 days after the last study treatment.
Adverse Event Reporting Description The data display threshold for SAEs is set to 1% or more, that of AEs is set to 5% or more.
Arm/Group Title Pacritinib Best Available Therapy
Arm/Group Description Pacritinib 400 mg QD BAT includes any physician-selected treatment for primary or secondary myelofibrosis with the exclusion of JAK inhibitors (inhibitors of Janus kinases).
All Cause Mortality
Pacritinib Best Available Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 27/220 (12.3%) 3/106 (2.8%)
Serious Adverse Events
Pacritinib Best Available Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 117/220 (53.2%) 33/106 (31.1%)
Blood and lymphatic system disorders
Anemia 16/220 (7.3%) 20 5/106 (4.7%) 106
Thrombocytopenia 4/220 (1.8%) 4 0/106 (0%) 0
Febrile Neutropenia 3/220 (1.4%) 4 0/106 (0%) 0
Cardiac disorders
Cardiac failure congestive 4/220 (1.8%) 6 1/106 (0.9%) 1
Atrial fibrillation 3/220 (1.4%) 3 1/106 (0.9%) 1
Cardiac Failure 7/220 (3.2%) 7 3/106 (2.8%) 3
Gastrointestinal disorders
Diarrhoea 4/220 (1.8%) 5 2/106 (1.9%) 2
Abdominal Pain 3/220 (1.4%) 3 0/106 (0%) 0
Vomiting 3/220 (1.4%) 3 0/106 (0%) 0
General disorders
Disease Progression 6/220 (2.7%) 6 3/106 (2.8%) 3
Pyrexia 6/220 (2.7%) 6 3/106 (2.8%) 4
Multi-organ failure 3/220 (1.4%) 3 0/106 (0%) 0
Infections and infestations
Pneumonia 16/220 (7.3%) 21 4/106 (3.8%) 4
Lobar pneumonia 4/220 (1.8%) 4 0/106 (0%) 0
Lower Respiratory Tract Infection 3/220 (1.4%) 3 1/106 (0.9%) 1
Sepis 2/220 (0.9%) 3 2/106 (1.9%) 2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell Carcinoma 6/220 (2.7%) 6 2/106 (1.9%) 2
Squarmous cell Carcinoma 4/220 (1.8%) 10 1/106 (0.9%) 1
Acute myeloid leukaemia 3/220 (1.4%) 3 0/106 (0%) 0
Squamous cell carcinoma of skin 3/220 (1.4%) 7 1/106 (0.9%) 1
Clonal evolution 1/220 (0.5%) 1 0/106 (0%) 0
Endometrial cancer 1/220 (0.5%) 1 0/106 (0%) 0
Epstein-Barr virus associated lymphoma 1/220 (0.5%) 1 0/106 (0%) 0
Renal and urinary disorders
Renal Failure Acute 4/220 (1.8%) 4 0/106 (0%) 0
Respiratory, thoracic and mediastinal disorders
Epistaxis 5/220 (2.3%) 5 0/106 (0%) 0
Dyspnoea 2/220 (0.9%) 2 4/106 (3.8%) 5
Other (Not Including Serious) Adverse Events
Pacritinib Best Available Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 207/220 (94.1%) 81/106 (76.4%)
Blood and lymphatic system disorders
Anaemia 58/220 (26.4%) 58 18/106 (17%) 18
Thrombocytopenia 48/220 (21.8%) 48 15/106 (14.2%) 15
Neutropenia 12/220 (5.5%) 12 0/106 (0%) 0
Gastrointestinal disorders
Diarrhoea 142/220 (64.5%) 142 14/106 (13.2%) 14
Nausea 70/220 (31.8%) 70 7/106 (6.6%) 7
Vomiting 46/220 (20.9%) 46 7/106 (6.6%) 7
Abdominal pain 29/220 (13.2%) 29 11/106 (10.4%) 11
Constipation 22/220 (10%) 22 8/106 (7.5%) 8
General disorders
Fatigue 33/220 (15%) 33 9/106 (8.5%) 9
Oedema peripheral 24/220 (10.9%) 24 16/106 (15.1%) 16
Pyrexia 17/220 (7.7%) 17 11/106 (10.4%) 11
Asthernia 16/220 (7.3%) 16 7/106 (6.6%) 7
Infections and infestations
Upper respiratory tract infection 16/220 (7.3%) 16 6/106 (5.7%) 6
Urinary tract infection 12/220 (5.5%) 12 0/106 (0%) 0
Injury, poisoning and procedural complications
Contusion 11/220 (5%) 11 0/106 (0%) 0
Investigations
Electrocardiogram QT prolonged 12/220 (5.5%) 12 0/106 (0%) 0
Metabolism and nutrition disorders
Decreased appetite 21/220 (9.5%) 21 0/106 (0%) 0
Nervous system disorders
Headache 12/220 (5.5%) 12 0/106 (0%) 0
Psychiatric disorders
Insomnia 13/220 (5.9%) 13 0/106 (0%) 0
Respiratory, thoracic and mediastinal disorders
Dyspnoea 20/220 (9.1%) 20 9/106 (8.5%) 9
Epistaxis 17/220 (7.7%) 17 10/106 (9.4%) 10
Cough 18/220 (8.2%) 18 8/106 (7.5%) 8
Oropharyngeal 13/220 (5.9%) 13 0/106 (0%) 0
Skin and subcutaneous tissue disorders
Pruritus 14/220 (6.4%) 14 0/106 (0%) 0
Rush 12/220 (5.5%) 12 0/106 (0%) 0
Arthralgia 13/220 (5.9%) 13 0/106 (0%) 0
Pain in extremity 11/220 (5%) 11 9/106 (8.5%) 9
Vascular disorders
Hypertension 11/220 (5%) 11 0/106 (0%) 0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Results Point of Contact

Name/Title Beth Ziemba
Organization CTI BioPharma Corp.
Phone 206-272-4347
Email bziemba@ctibiopharma.com
Responsible Party:
CTI BioPharma
ClinicalTrials.gov Identifier:
NCT01773187
Other Study ID Numbers:
  • PERSIST-1 (PAC325)
First Posted:
Jan 23, 2013
Last Update Posted:
Sep 29, 2020
Last Verified:
Sep 1, 2020