Pacritinib Versus Best Available Therapy to Treat Myelofibrosis
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
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
- 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
- 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
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
- PERSIST-1 (PAC325)
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
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 |
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
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 |
bziemba@ctibiopharma.com |
- PERSIST-1 (PAC325)