Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis
Conditions
Keywords
Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis, Primary Myelofibrosis, Polycythemia Vera, Essential Thrombocythemia, Bone Marrow Disease, Hematologic Disease, Splenomegaly, Pacritinib, MPN-SAF, MPN-SAF TSS, Anemia, Myeloproliferative Neoplasm, Spleen volume, Thrombocytopenia, SB1518
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.
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.
Interventions
DRUGPacritinib
Sponsors
CTI BioPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, Belgium, Czechia, France, Germany, Hungary, Italy, Netherlands, New Zealand, Russia, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pacritinib Pacritinib 400 mg QD | 220 |
| Best Available Therapy BAT includes any physician-selected treatment for primary or secondary myelofibrosis with the exclusion of JAK inhibitors (inhibitors of Janus kinases). | 107 |
| Total | 327 |
Baseline characteristics
| Characteristic | Best Available Therapy | Total | Pacritinib |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 55 Participants | 190 Participants | 135 Participants |
| Age, Categorical Between 18 and 65 years | 52 Participants | 137 Participants | 85 Participants |
| Age, Continuous | 64.8 years STANDARD_DEVIATION 9.12 | 65.3 years STANDARD_DEVIATION 10.31 | 65.5 years STANDARD_DEVIATION 10.85 |
| Region of Enrollment Australia | 17 participants | 46 participants | 29 participants |
| Region of Enrollment Belgium | 1 participants | 9 participants | 8 participants |
| Region of Enrollment Czechia | 9 participants | 18 participants | 9 participants |
| Region of Enrollment France | 9 participants | 35 participants | 26 participants |
| Region of Enrollment Germany | 2 participants | 4 participants | 2 participants |
| Region of Enrollment Hungary | 21 participants | 70 participants | 49 participants |
| Region of Enrollment Italy | 10 participants | 21 participants | 11 participants |
| Region of Enrollment Netherlands | 8 participants | 21 participants | 13 participants |
| Region of Enrollment New Zealand | 4 participants | 20 participants | 16 participants |
| Region of Enrollment Russia | 18 participants | 53 participants | 35 participants |
| Region of Enrollment United Kingdom | 6 participants | 25 participants | 19 participants |
| Region of Enrollment United States | 2 participants | 5 participants | 3 participants |
| Sex: Female, Male Female | 47 Participants | 142 Participants | 95 Participants |
| Sex: Female, Male Male | 60 Participants | 185 Participants | 125 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 27 / 220 | 3 / 106 |
| other Total, other adverse events | 207 / 220 | 81 / 106 |
| serious Total, serious adverse events | 117 / 220 | 33 / 106 |
Outcome results
Primary
Spleen Volume Reduction
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pacritinib | Spleen Volume Reduction | 42 Participants |
| Best Available Therapy | Spleen Volume Reduction | 5 Participants |
Comparison: Pre-specifiedp-value: 0.0003Fisher Exact
Secondary
Total Symptom Score (TSS) Reduction
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
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pacritinib | Total Symptom Score (TSS) Reduction | 19 Participants |
| Best Available Therapy | Total Symptom Score (TSS) Reduction | 5 Participants |
Comparison: Pre-specifiedp-value: 0.2368Fisher Exact