Post-Essential Thrombocytopenia, Post-Polycythemia Vera, Primary Myelofibrosis
Conditions
Keywords
Bone marrow, Myelofibrosis, JAK2mutation, Post-Polycythemia Vera, Post-Essential Thrombocytopenia
Brief summary
This study assessed the safety and efficacy of Panobinostat as a single agent in the treatment of Primary Myelofibrosis, Post-Polycythemia Vera and Post-Essential Thrombocythemia. There were two cohorts - participants with JAK2 mutation and participants without JAK2 mutation.
Interventions
DRUGPanobinostat
Panobinostat oral capsules
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of myelofibrosis, either primary myelofibrosis (PMF), post- polycythemia vera (PV) or post-essential thrombocythemia (ET) myelofibrosis (MF) with international prognostic scoring system (IPSS) score of 2 (intermediate risk) or 3 (high risk) plus at least one of the following: Symptomatic spenomegaly (≥10 centimeter \[cm\] below costal margin \[BCM\]) Hemoglobin \< 10 or red cell transfusion dependent. (The presence of a janus kinase (JAK2) V617F mutation is not required for study entry). 2. Participants must meet the following laboratory criteria: * Participants can be either JAK2 V617F mutated or wild type. * Serum potassium, magnesium, phosphorous, sodium, total calcium (corrected for serum albumin) or ionized calcium within normal limits (WNL) for the institution Note: Potassium, magnesium, phosphorous, sodium, and/or calcium supplements maybe given to correct values that are \< lower limit of normal (LLN). Post correction values must not be deemed to be a clinically significant abnormality prior to participants being dosed. * Creatinine \< 1.5 X upper limit of normal (ULN) or calculated creatinine clearance (CrCl) ≥ 50 milliliter per minute (mL/min) (modification of diet in renal diseases \[MDRD\] formula). * Aspartate aminotransferase \[AST\] and alanine transaminase \[ALT\] ≤ 2.5 x ULN. * Serum total bilirubin ≤ 1.5 x ULN. 3. Eastern cooperative oncology group (ECOG) performance status of ≤ 2. 4. Clinically euthyroid. Note: Participants are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism.
Exclusion criteria
1. Prior histone deacetylases (HDAC), deacetylase (DAC), heat shock protein 90 (HSP90) inhibitors or valproic acid for the treatment of cancer. 2. Previous treatment with JAK2 inhibitors. 3. Any participant who has previously received radiation therapy to ≥ 30% of the bone marrow. 4. Impaired cardiac function or clinically significant cardiac diseases. 5. Participant with unresolved diarrhoea ≥ grade 2. 6. Participants using medications that have a relative risk of prolonging the QT interval or inducing Torsade de pointes if treatment cannot be discontinued or switched to a different medication prior to starting study drug. 7. Participants who have undergone major surgery ≤ 4 weeks prior to starting study drug or who have not recovered from side effects of surgery. 8. Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not using an effective method of birth control. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential must have a negative serum pregnancy test at screening and at baseline. 9. Male participants whose sexual partners are WOCBP not using effective birth control. 10. Participants with a prior malignancy with in the last 5 years (except for basal or squamous cell carcinoma, or in situ cancer of the cervix). 11. Participants with known positivity for human immunodeficiency virus (HIV) or hepatitis C; baseline testing for HIV and hepatitis C is not required. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response (OR) Rate Per International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria | Up to approximately 2 years | Overall response (OR) = Complete remission (CR) + Partial remission (PR) + Clinical improvement (CI). CR: complete resolution of disease-related symptoms and signs with hemoglobin level 110 grams per deciliter (g/L), platelet count 100 x 10\^9/liter (L), and absolute neutrophil count (ANC) 1.0 x 10\^9/L, all 3 blood counts \< upper normal limit (UNL), normal leukocyte differential, and bone marrow histologic remission. PR= all of the criteria for CR except the requirement for bone marrow histologic remission. CI= minimum 20 g/L increase in hemoglobin for transfusion or becoming transfusion independent or reduction in splenomegaly ≥ 50% or 100% increase in platelet count and absolute platelet count of 50 x 10\^9/L and 100% increase in ANC of at least 0.5 x 10\^9/L. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Baseline, Cycle 6 (each cycle was of 28 days) | The MF-SAF consists of seven questions about key symptoms and impact of MF. Questions were scored on a scale of 0-10, with higher scores indicating more severe symptoms and greater inactivity. Questions 1-6 investigate the following symptoms: night sweats, pruritus/itching, abdominal discomfort, pain under the ribs, early satiety and bone/muscle pain. Question 7 asked participants to report levels of inactivity. Negative change from baseline indicates improvement. |
| Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Baseline, Cycles 2, and 4 (each cycle was of 28-days) | The MF-SAF consists of seven questions about key symptoms and impact of MF. Questions were scored on a scale of 0-10, with higher scores indicating more severe symptoms and greater inactivity. Questions 1-6 investigate the following symptoms: night sweats, pruritus/itching, abdominal discomfort, pain under the ribs, early satiety and bone/muscle pain. Question 7 asked participants to report levels of inactivity. Negative change from baseline indicates improvement. |
| Number of Participants With Adverse Events (AEs), and Serious Adverse Events (SAEs) | AE: From the start of treatment up to 28 days after last study dose (up to approximately 2 years); SAE: From time of informed consent up to 4 weeks after last study dose (approximately 2 years) | An adverse event is the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. SAEs was an undesirable sign, symptom or medical condition which is: life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, requires hospitalizations or prolongation of hospitalizations, or is medically significant |
Other
| Measure | Time frame |
|---|---|
| Monthly Capsule Counts to Assess Compliance to Panobinostat Treatment | Up to approximately 2 years |
| To Compare the Response to Panobinostat in Patients With the JAK2 V617F Mutation to Those Without the JAK2 V617F Mutation | Up to approximately 2 years |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at 9 investigative centers in the United States from 31 August 2009 to 29 August 2011.
Participants by arm
| Arm | Count |
|---|---|
| Panobinostat Participants received panobinostat 40 mg, capsules, orally, with or without food, three times a week on Monday, Wednesday, and Friday for up to 6 treatment cycles (each cycle of 28-days) with dose adjustments possible. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Abnormal Laboratory Value (s) | 2 |
| Overall Study | Administrative Problems | 5 |
| Overall Study | Adverse Event (s) | 11 |
| Overall Study | Death | 1 |
| Overall Study | Disease Progression | 3 |
| Overall Study | Subject withdrew consent | 13 |
Baseline characteristics
| Characteristic | Panobinostat |
|---|---|
| Age, Continuous | 68.3 years STANDARD_DEVIATION 10.3 |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 35 |
| other Total, other adverse events | 35 / 35 |
| serious Total, serious adverse events | 19 / 35 |
Outcome results
Primary
Overall Response (OR) Rate Per International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria
Overall response (OR) = Complete remission (CR) + Partial remission (PR) + Clinical improvement (CI). CR: complete resolution of disease-related symptoms and signs with hemoglobin level 110 grams per deciliter (g/L), platelet count 100 x 10\^9/liter (L), and absolute neutrophil count (ANC) 1.0 x 10\^9/L, all 3 blood counts \< upper normal limit (UNL), normal leukocyte differential, and bone marrow histologic remission. PR= all of the criteria for CR except the requirement for bone marrow histologic remission. CI= minimum 20 g/L increase in hemoglobin for transfusion or becoming transfusion independent or reduction in splenomegaly ≥ 50% or 100% increase in platelet count and absolute platelet count of 50 x 10\^9/L and 100% increase in ANC of at least 0.5 x 10\^9/L.
Time frame: Up to approximately 2 years
Population: FAS population included all participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Panobinostat | Overall Response (OR) Rate Per International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) Criteria | 2.9 percentage of participants |
Secondary
Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores
The MF-SAF consists of seven questions about key symptoms and impact of MF. Questions were scored on a scale of 0-10, with higher scores indicating more severe symptoms and greater inactivity. Questions 1-6 investigate the following symptoms: night sweats, pruritus/itching, abdominal discomfort, pain under the ribs, early satiety and bone/muscle pain. Question 7 asked participants to report levels of inactivity. Negative change from baseline indicates improvement.
Time frame: Baseline, Cycles 2, and 4 (each cycle was of 28-days)
Population: FAS population included all participants who received at least one dose of study drug.~All 35 participants were evaluated for this Outcome. The Number Analyzed represented in each row differs from the Overall Number of Participants Analyzed as scores that are presented are for the participants who reported the measured event at the time evaluated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Fatigue Right now | 0.0 score on a scale | Standard Deviation 2 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Fatigue Worst Past 24 Hours | 0.7 score on a scale | Standard Deviation 1.98 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: General Activity | 0.0 score on a scale | Standard Deviation 2.03 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Mood | 0.5 score on a scale | Standard Deviation 2.15 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Walking Ability | -0.6 score on a scale | Standard Deviation 2.86 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Normal Work | 0.2 score on a scale | Standard Deviation 2.87 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Relations with Other People | -0.1 score on a scale | Standard Deviation 2.71 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Cough | -0.1 score on a scale | Standard Deviation 2.07 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Bone Pain | -1.0 score on a scale | Standard Deviation 2.79 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Inactivity | 0.6 score on a scale | Standard Deviation 3.25 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Cough | -0.9 score on a scale | Standard Deviation 1.36 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Bone Pain | -1.8 score on a scale | Standard Deviation 3.41 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Fatigue Usual Past 24 Hours | 0.5 score on a scale | Standard Deviation 1.83 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Enjoyment of Life | 0.3 score on a scale | Standard Deviation 3.3 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Filling up quickly when you eat | 0.7 score on a scale | Standard Deviation 2.38 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Abdominal Pain or Discomfort | -0.0 score on a scale | Standard Deviation 2.64 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Inactivity | 0.8 score on a scale | Standard Deviation 2.45 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Night Sweats | -1.0 score on a scale | Standard Deviation 2.36 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: Itching | -1.5 score on a scale | Standard Deviation 2.89 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 2, Day 1: What is Overall Quality of Life? | -0.4 score on a scale | Standard Deviation 2.24 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Fatigue Right now | 0.0 score on a scale | Standard Deviation 1.93 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Fatigue Usual Past 24 Hours | 0.8 score on a scale | Standard Deviation 1.91 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Fatigue Worst Past 24 Hours | 1.0 score on a scale | Standard Deviation 1.31 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: General Activity | -0.5 score on a scale | Standard Deviation 3.07 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Mood | 0.3 score on a scale | Standard Deviation 2.75 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Walking Ability | -0.6 score on a scale | Standard Deviation 3.26 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Normal Work | 0.9 score on a scale | Standard Deviation 2.53 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Relations with Other People | -0.6 score on a scale | Standard Deviation 2.2 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Enjoyment of Life | 0.4 score on a scale | Standard Deviation 3.62 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Filling up quickly when you eat | -0.1 score on a scale | Standard Deviation 4.42 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Abdominal Pain or Discomfort | 1.0 score on a scale | Standard Deviation 2.67 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Night Sweats | -1.1 score on a scale | Standard Deviation 3.52 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: Itching | -0.1 score on a scale | Standard Deviation 0.9 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores | Cycle 4, Day 1: What is Overall Quality of Life? | -0.3 score on a scale | Standard Deviation 1.6 |
Secondary
Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6
The MF-SAF consists of seven questions about key symptoms and impact of MF. Questions were scored on a scale of 0-10, with higher scores indicating more severe symptoms and greater inactivity. Questions 1-6 investigate the following symptoms: night sweats, pruritus/itching, abdominal discomfort, pain under the ribs, early satiety and bone/muscle pain. Question 7 asked participants to report levels of inactivity. Negative change from baseline indicates improvement.
Time frame: Baseline, Cycle 6 (each cycle was of 28 days)
Population: FAS population included all participants who received at least one dose of study drug.~All 35 participants were evaluated for this Outcome. The Number Analyzed represented in each row differs from the Overall Number of Participants Analyzed as scores that are presented are for the participants who reported the measured event at the time evaluated.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Walking Ability | -3.0 score on a scale | Standard Deviation 5.66 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: What is Overall Quality of Life? | -2.5 score on a scale | Standard Deviation 2.12 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Fatigue Right now | -1.5 score on a scale | Standard Deviation 2.12 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Fatigue Usual Past 24 Hours | -1.0 score on a scale | Standard Deviation 5.66 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Fatigue Worst Past 24 Hours | -3.0 score on a scale | Standard Deviation 2.83 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: General Activity | -3.5 score on a scale | Standard Deviation 2.12 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Mood | -3.5 score on a scale | Standard Deviation 3.54 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Normal Work | -4.0 score on a scale | Standard Deviation 4.24 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Relations with Other People | -4.5 score on a scale | Standard Deviation 2.12 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Enjoyment of Life | -5.0 score on a scale | Standard Deviation 4.24 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Filling up quickly when you eat | 1.0 score on a scale | Standard Deviation 1.41 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Abdominal pain or Discomfort | 0.5 score on a scale | Standard Deviation 2.12 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Inactivity | -0.5 score on a scale | Standard Deviation 3.54 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Cough | -1.5 score on a scale | Standard Deviation 2.12 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Night Sweats | -0.5 score on a scale | Standard Deviation 0.71 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Itching | 1.5 score on a scale | Standard Deviation 2.12 |
| Panobinostat | Change From Baseline in Myelofibrosis Symptom Assessment Form (MF-SAF) Scale Scores At Cycle 6 | Cycle 6, Day 1: Bone Pain | -2.5 score on a scale | Standard Deviation 0.71 |
Secondary
Number of Participants With Adverse Events (AEs), and Serious Adverse Events (SAEs)
An adverse event is the appearance or worsening of any undesirable sign, symptom, or medical condition occurring after starting the study drug even if the event is not considered to be related to study drug. SAEs was an undesirable sign, symptom or medical condition which is: life-threatening, persistent or significant disability/incapacity, congenital anomaly/birth defect, requires hospitalizations or prolongation of hospitalizations, or is medically significant
Time frame: AE: From the start of treatment up to 28 days after last study dose (up to approximately 2 years); SAE: From time of informed consent up to 4 weeks after last study dose (approximately 2 years)
Population: Safety set population included all participants who received at least one dose of study drug and had at least one post-baseline safety assessment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Panobinostat | Number of Participants With Adverse Events (AEs), and Serious Adverse Events (SAEs) | AEs | 35 Participants |
| Panobinostat | Number of Participants With Adverse Events (AEs), and Serious Adverse Events (SAEs) | SAEs | 19 Participants |
Other Pre-specified
Monthly Capsule Counts to Assess Compliance to Panobinostat Treatment
Time frame: Up to approximately 2 years
Other Pre-specified
To Compare the Response to Panobinostat in Patients With the JAK2 V617F Mutation to Those Without the JAK2 V617F Mutation
Time frame: Up to approximately 2 years