Myelofibrosis, Polycythemia Vera, Thrombocythemia
Conditions
Keywords
Myelofibrosis, Post-PV Myelofibrosis, Post-ET Myelofibrosis, LIMBER, LIMBER-213, MF, Myeloproliferative Neoplasms
Brief summary
This is a 2-part study. In Part 1, participants will be dosed at 2 different dose levels in order to select the RP2D for Part 2 of the study.
Interventions
DRUGitacitinib
itacitinb Immediate Release (IR) will be dosed orally twice a day
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of primary MF meeting the 2016 WHO criteria for overt PMF or secondary MF (PPV-MF or PET-MF) meeting the 2008 IWG-MRT criteria. * At least Intermediate 1 risk MF according to the DIPSS. * Prior treatment with ruxolitinib and/or fedratinib monotherapy * Currently receiving ruxolitinib or fedratinib monotherapy for PMF or secondary MF. * Splenomegaly defined as palpable spleen at least 5 cm below the left costal margin or volume ≥ 450 cm3 on imaging assessed during screening. * Allogeneic stem cell transplant not planned. * Platelet is greater than or equal to 50 × 109/L at screening. * Ability to comprehend and willingness to sign a written ICF for the study. * Willingness to avoid pregnancy or fathering children.
Exclusion criteria
* Prior treatment with a JAK inhibitor other than ruxolitinib or fedratinib * Record of ≥ 10% myeloid blasts in the peripheral blood (on peripheral blood smear) or bone marrow prior to or at the time of screening * For participants on ruxolitinib or fedratinib, unable to be tapered from that treatment over the course of 14 days without corticosteroids, hydroxyurea, or other agents * Treatment with ruxolitinib, fedratinib or other MF-directed therapy (approved or investigational) within 2 weeks of Day 1 * Prior splenectomy or splenic irradiation within 6 months before receiving the first dose of itacitinib * Unable or unwilling to undergo serial MRI or CT scans for spleen volume measurement * Unable or unwilling to complete MFSAF v4.0 diary on a daily basis during the study * ECOG performance status ≥ 3 * Life expectancy less than 24 weeks * Not willing to receive RBC or platelet transfusions * Participants with laboratory values at screening outside of protocol defined ranges * Significant concurrent, uncontrolled medical condition * Participants with impaired cardiac function or clinically significant cardiac disease unless approved by medical monitor/sponsor * History or presence of an abnormal ECG that, in the investigator's opinion, is clinically meaningful * Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment. * Evidence of HBV or HCV infection or risk of reactivation * Known HIV infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | up to 724 days | An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. |
| Part 1: Number of Participants With Any Grade 3 or Higher TEAE | up to 724 days | A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal. |
| Part 2: Splenic Response Rate (SRR) at Week 24 | Baseline; Week 24 | SRR was defined as the percentage of participants who had a reduction in spleen volume (by imaging) of at least 35% when compared with Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Mean Change (From Day 1 Versus Week 12 and Week 24) in the 5 Multi-item Functional Scale Scores and the Multi-item Global Health Status Scale Score (EORTC QLQ-C30) | Baseline; Weeks 12 and 24 | The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) was to be used to assess the improvement in quality of life. |
| Part 2: Number of Participants With Any TEAE | up to at least 24 weeks | An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. |
| Part 2: Percentage of Participants Categorized as Improved on the Week 24 Patient Global Impression of Change (PGIC) | Baseline; Week 24 | The PGIC consists of a single question pertaining to a participant's overall status since the start of the study. The questionnaire gives participants 7 options to describe their overall status including: very much improved, much improved, minimally improved, no change, minimally worse, much worse, and very much worse. |
| Part 2: Number of Participants With Any Grade 3 or Higher TEAE | up to at least 24 weeks | A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal. |
| Part 2: Total Symptom Score (TSS) Response Rate at Week 24 | Baseline; Week 24 | TSS response was defined as the percentage of participants who achieved at least 50% reduction in TSS over the 28 days immediately before the end of Week 24 compared with the 7 days immediately before the initiation of itacitinib immediate release (aseline).B |
Countries
Austria, Belgium, Germany, Italy, Poland, Spain, United States
Participant flow
Pre-assignment details
This study was conducted at 3 study centers in the United States and Italy.
Participants by arm
| Arm | Count |
|---|---|
| Itacitinib 300 mg Participants received itacitinib immediate release 300 milligrams (mg) twice a day (BID) orally (PO) for at least 24 weeks. Participants could remain on treatment as long as they were receiving clinical benefit and had not met any criteria for treatment discontinuation. | 4 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 2 |
| Overall Study | Protocol-specified withdrawal criterion met | 1 |
Baseline characteristics
| Characteristic | Itacitinib 300 mg |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 4 | 2 / 4 |
| other Total, other adverse events | 4 / 4 | 4 / 4 |
| serious Total, serious adverse events | 3 / 4 | 3 / 4 |
Outcome results
Primary
Part 1: Number of Participants With Any Grade 3 or Higher TEAE
A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.
Time frame: up to 724 days
Population: Safety Evaluable Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Itacitinib 300 mg | Part 1: Number of Participants With Any Grade 3 or Higher TEAE | 4 Participants |
Primary
Part 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment.
Time frame: up to 724 days
Population: Safety Evaluable Population: all participants enrolled in the study who received at least 1 dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Itacitinib 300 mg | Part 1: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | 4 Participants |
Primary
Part 2: Splenic Response Rate (SRR) at Week 24
SRR was defined as the percentage of participants who had a reduction in spleen volume (by imaging) of at least 35% when compared with Baseline.
Time frame: Baseline; Week 24
Population: Analysis was not conducted because Part 2 never opened for enrollment.
Secondary
Part 2: Mean Change (From Day 1 Versus Week 12 and Week 24) in the 5 Multi-item Functional Scale Scores and the Multi-item Global Health Status Scale Score (EORTC QLQ-C30)
The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) was to be used to assess the improvement in quality of life.
Time frame: Baseline; Weeks 12 and 24
Population: Analysis was not conducted because Part 2 never opened for enrollment.
Secondary
Part 2: Number of Participants With Any Grade 3 or Higher TEAE
A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grades 1 through 5. The investigator made an assessment of intensity for each AE and SAE reported during the study and assigned it to 1 of the following categories: Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; treatment not indicated. Grade 2: moderate; minimal, local, or noninvasive treatment indicated; limiting age-appropriate activities of daily living. Grade 3: severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent treatment indicated. Grade 5: fatal.
Time frame: up to at least 24 weeks
Population: Analysis was not conducted because Part 2 never opened for enrollment.
Secondary
Part 2: Number of Participants With Any TEAE
An adverse event was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not it was considered drug-related. An AE could therefore have been any unfavorable or unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as an AE that was reported for the first time or the worsening of a pre-existing event after the first dose of study treatment.
Time frame: up to at least 24 weeks
Population: Analysis was not conducted because Part 2 never opened for enrollment.
Secondary
Part 2: Percentage of Participants Categorized as Improved on the Week 24 Patient Global Impression of Change (PGIC)
The PGIC consists of a single question pertaining to a participant's overall status since the start of the study. The questionnaire gives participants 7 options to describe their overall status including: very much improved, much improved, minimally improved, no change, minimally worse, much worse, and very much worse.
Time frame: Baseline; Week 24
Population: Analysis was not conducted because Part 2 never opened for enrollment.
Secondary
Part 2: Total Symptom Score (TSS) Response Rate at Week 24
TSS response was defined as the percentage of participants who achieved at least 50% reduction in TSS over the 28 days immediately before the end of Week 24 compared with the 7 days immediately before the initiation of itacitinib immediate release (aseline).B
Time frame: Baseline; Week 24
Population: Analysis was not conducted because Part 2 never opened for enrollment.