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 Diseases, Hemorrhagic Disorders, 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 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.
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) * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Australia, Belgium, Canada, Czechia, France, Germany, Hungary, Netherlands, New Zealand, Russia, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pacritinib, Once Daily Pacritinib 400 mg, once daily | 104 |
| Pacritinib, Twice Daily Pacritinib 200 mg, twice daily | 107 |
| 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. | 100 |
| Total | 311 |
Baseline characteristics
| Characteristic | Pacritinib, Twice Daily | Pacritinib, Once Daily | Total | Best Available Therapy |
|---|---|---|---|---|
| Age, Categorical <=18 years | 41 Participants | 32 Participants | 105 Participants | 32 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 65 Participants | 70 Participants | 203 Participants | 68 Participants |
| Age, Continuous | 65.9 years STANDARD_DEVIATION 8.75 | 69 years STANDARD_DEVIATION 8.55 | 67.2 years STANDARD_DEVIATION 9.01 | 66.9 years STANDARD_DEVIATION 9.75 |
| Region of Enrollment Australia | 5 Participants | 4 Participants | 13 Participants | 4 Participants |
| Region of Enrollment Belgium | 2 Participants | 2 Participants | 5 Participants | 1 Participants |
| Region of Enrollment Canada | 2 Participants | 5 Participants | 11 Participants | 4 Participants |
| Region of Enrollment Czechia | 4 Participants | 2 Participants | 11 Participants | 5 Participants |
| Region of Enrollment France | 10 Participants | 8 Participants | 27 Participants | 9 Participants |
| Region of Enrollment Germany | 4 Participants | 10 Participants | 17 Participants | 3 Participants |
| Region of Enrollment Hungary | 8 Participants | 9 Participants | 24 Participants | 7 Participants |
| Region of Enrollment Netherlands | 1 Participants | 0 Participants | 2 Participants | 1 Participants |
| Region of Enrollment New Zealand | 6 Participants | 4 Participants | 13 Participants | 3 Participants |
| Region of Enrollment Russia | 10 Participants | 11 Participants | 30 Participants | 9 Participants |
| Region of Enrollment United Kingdom | 11 Participants | 5 Participants | 27 Participants | 11 Participants |
| Region of Enrollment United States | 44 Participants | 44 Participants | 131 Participants | 43 Participants |
| Sex: Female, Male Female | 44 Participants | 51 Participants | 140 Participants | 45 Participants |
| Sex: Female, Male Male | 63 Participants | 53 Participants | 171 Participants | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 22 / 104 | 20 / 107 | 20 / 100 |
| other Total, other adverse events | 104 / 104 | 100 / 106 | 87 / 98 |
| serious Total, serious adverse events | 48 / 104 | 50 / 106 | 30 / 98 |
Outcome results
Primary
Spleen Volume Reduction
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).
Time frame: Baseline to Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pacritinib, Once Daily | Spleen Volume Reduction | 11 Participants |
| Pacritinib, Twice Daily | Spleen Volume Reduction | 16 Participants |
| Best Available Therapy | Spleen Volume Reduction | 2 Participants |
Comparison: BAT arm compared to pooled pacritinib arms (QD + BID - ITT Efficacy)p-value: 0.0011Fisher Exact
p-value: 0.0173Fisher Exact
p-value: 0.0007Fisher Exact
Primary
Total Symptom Score (TSS) Reduction
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.
Time frame: Baseline to Week 24
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pacritinib, Once Daily | Total Symptom Score (TSS) Reduction | 13 Participants |
| Pacritinib, Twice Daily | Total Symptom Score (TSS) Reduction | 24 Participants |
| Best Available Therapy | Total Symptom Score (TSS) Reduction | 10 Participants |
Comparison: BAT arm compared to pooled pacritinib arms (QD + BID - ITT Efficacy)p-value: 0.0791Fisher Exact
p-value: 0.6524Fisher Exact
p-value: 0.0106Fisher Exact