Myelofibrosis With Myeloid Metaplasia, Myeloid Metaplasia, Myelofibrosis
Conditions
Keywords
Celgene, CC-4047, Myelofibrosis, myelofibrosis with myeloid metaplasia, myeloid metaplasia, JAK2, CC-4047-MMM-001, Prednisone, Phase II, pomalidomide, bone marrow histology, imids, MMM, Ashkenazi Jewish Population, exposure to Thorotrast, exposure to solvents (benzene and toluene), acute megakaryocytic leukemia, history of polycythemia vera
Brief summary
The purpose of this study is to determine the safety of and to select a treatment regimen of pomalidomide (CC-4047) either as single-agent or in combination with prednisone to study further in patients with myelofibrosis with myeloid metaplasia (MMM).
Detailed description
Participants received study treatment in the Double Blind Treatment Phase for up to 12 cycles (336 days; 12 cycles of 28 days each). Participants who completed the Double-Blind Treatment Phase were unblinded and, if receiving pomalidomide and determined to have a complete remission (CR), partial remission (PR) or clinical improvement (CI) using the International Working Group (IWG) Response Criteria in the study protocol, could have continued on their current dose of pomalidomide until disease progression. Participants receiving placebo were discontinued from the study.
Interventions
DRUGPomalidomide
DRUGPrednisone
Participants will take oral prednisone in the evening for 3 cycles of 28 days each (up to 84 days). The dose will be as follows: 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day.
DRUGPlacebo to pomalidomide
Matching pomalidomide placebo tablets
Matching prednisone placebo tablets
Sponsors
Celgene
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must sign an informed consent form * Must be \>18 years of age * Must be diagnosed with myelofibrosis * Eligibility is based on local pathology review of bone marrow aspirate and biopsy * Screening total hemoglobin level \< 10g/dL or transfusion-dependent anemia defined as per International Working Group (IWG) criteria. * Must have adequate organ function as demonstrated by the following ≤ 14 days prior to starting study drug: * Alanine aminotransferase (ALT; SGPT)/aspartate aminotransferase (AST; SGOT) ≤ 3 x upper limit of normal (ULN), \[unless upon judgment of the treating physician, it is believed to be due to extra-medullary hematopoiesis (EMH)\]. * Total Bilirubin \<3x ULN or Direct Bilirubin \<2 x ULN * Serum creatinine ≤ 2.0 mg/dL * Absolute neutrophil count ≥ 1,000/μL (≥ 1 x 10\^9/L). * Platelet count ≥ 50,000 /μL (≥ 50 x 10\^9/L). * Patients must be willing to receive transfusion of blood products * Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2 at screening. * Must be able to adhere to the study visit schedule and other protocol requirements. * No active malignancies with the exception of controlled prostate cancer, basal cell or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or breast. * Must agree to follow pregnancy precautions as required per the protocol
Exclusion criteria
* Known positive status for human immunodeficiency virus (HIV), hepatitis B carrier, or active hepatitis C infection. * Previous untoward reaction to corticosteroid (specifically, prednisone) therapy that was severe enough, in the opinion of the treating physician, to preclude study participation. * The use of any growth factors, cytotoxic chemotherapeutic agents (e.g. hydroxyurea and anagrelide), corticosteroids, or experimental drug or therapy within a minimum of 28 days of starting CC-4047 and/or lack of recovery from all toxicity from previous therapy to grade 1 or better (e.g. alpha interferon may require 84 days of longer or washout). * Prior therapy with CC-4047 or, lenalidomide or thalidomide for Myelofibrosis with myeloid metaplasia (MMM). (Prior prednisone use as a therapy for MMM is allowed, but not within 28 days of starting CC-4047). * History of deep vein thrombosis or pulmonary embolism within one year of starting study medication. * Any serious medical condition or psychiatric illness that would prevent, (as judged by the treating physician) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * Pregnant or lactating females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment | Up to 168 days | A clinical responder was defined as either: 1. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or 2. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or 3. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at \> 5 cm and became not palpable. Participants who discontinued the study early without achieving clinical response were counted as non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment | Up to 336 days | A clinical responder was defined as either: 1. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or 2. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or 3. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at \> 5 cm and became not palpable. Participants who discontinued the study early without achieving clinical response were counted as non-responders. |
| Time to the First Clinical Response | Up to 168 days | The time to the first clinical response achieved within 168 days after the first study drug dosing date was calculated for participants who achieved a clinical response as: Start date of the first clinical response - the first study drug date +1. A clinical responder was defined as either: 1. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or 2. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or 3. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at \> 5 cm and became not palpable. |
| Duration of First Clinical Response | Up to 40 months | For RBC-transfusion-dependent patients, duration of response was calculated as the last day of response - first day of response +1, where the last day of response was the date of the first RBC-transfusion administrated at or more than 56 days after the response started. For patients who did not receive a subsequent transfusion after the response started, the end date of response was censored at the day of last hemoglobin assessment. For RBC-transfusion-independent patients, the duration of response was calculated as the last day of response - first day of response +1, where the last day of response was the earlier of the date of a hemoglobin increase of \< 2.0 g/dL and the date of a RBC transfusion at ≥ 56 days after the response started. For patients whose hemoglobin measurements were always ≥ 2.0 g/dL and never received a RBC transfusion after response started, the end date of the response was censored at the date of last hemoglobin measurement. Kaplan-Meier methodology was used. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Baseline and Cycle 6 (168 days). | The FACT-An comprises the four subscales of the 27-item FACT-General Scale (FACT-G), Physical Well-being, Social/Family Well-being, Emotion Well-being, Functional Well-Being, and the Additional Concerns Anemia subscale. Questions are rated on a scale from 0 to 4, where higher scores indicate more impact on quality of life. * Physical Well-being consists of 7 questions, the subscale score ranges from 0-28; * Social/Family Well-being consists of 7 questions, the subscale score ranges from 0-28; * Emotion Well-being consists of 6 questions, the subscale score ranges from 0-24; * Functional Well-Being consists of 7 questions, the subscale score ranges from 0-28; * Anemia subscale consists of 20 questions, the subscale score ranges from 0-80; * Total FACT-An score ranges from 0-188. |
| Change From Baseline in Hemoglobin Concentration for Responders | Baseline, Cycle 6 (168 days) | Change from Baseline in hemoglobin for participants with a clinical response within the first 6 cycles of treatment. |
| Change From Baseline in Hemoglobin Concentration for Non-Responders | Baseline, Cycle 6 (168 days) | Change from Baseline in hemoglobin for participants without a clinical response within the first 6 cycles of treatment. |
| Change From Baseline in Likert Abdominal Pain Scale | Baseline and Cycle 6 (168 days) | Participants rated abdominal discomfort or pain over the previous week on a scale from zero to ten, where zero is no discomfort or pain and ten is the worst pain imaginable. |
| Percentage of Participants With Clinical Response by Baseline JAK2 Assessment | Up to 336 days | Percentage of participants who achieved a clinical response, presented by participants with positive and negative janus kinase 2 (JAK2) V617F mutation results at Baseline. |
| Number of Participants With Adverse Events (AEs) | From date of the first dose of the study drug until discontinuation or the data cut-off date (up to approximately 45 months). | A serious AE (SAE) was defined as any AE which resulted in death or was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or constituted an important medical event (events that may have jeopardized the patient or required intervention to prevent one of the outcomes listed above). The severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) or according to the following scale: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Death. The Investigator determined the relationship between study drug and the occurrence of an AE as Not Related or Related (since the study was double-blinded, a patient receiving only prednisone could have an AE that was judged as related to pomalidomide, and vice-versa). |
Countries
Austria, Italy, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Prednisone Participants received oral prednisone from Day 1-28 of each 28-day cycle for up to 3 cycles (84 days), 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day, and pomalidomide placebo tablets on Days 1-28 for up to 12 cycles in the Double-Blind Treatment Phase.
After the completion of cycle 12 and upon unblinding, participants were discontinued from the study. | 22 |
| Pomalidomide 2 mg Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and prednisone placebo tablets on Days 1-28 for the first 3 cycles in the Double-Blind Treatment Phase.
After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. | 22 |
| Pomalidomide 2 mg + Prednisone Participants received 2 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase.
After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. | 22 |
| Pomalidomide 0.5 mg + Prednisone Participants received 0.5 mg oral pomalidomide daily from Day 1-28 of each 28-day cycle for up to 12 cycles (336 days), and oral prednisone tablets on Days 1-28 for the first 3 cycles, 1st cycle = 30 mg daily, 2nd cycle = 15 mg daily, 3rd cycle = 15 mg every other day in the Double-Blind Treatment Phase.
After the completion of cycle 12 and upon unblinding, eligible participants continued to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle. Participants could remain on study treatment in the Extension Phase until disease progression, unacceptable toxicity or voluntary withdrawal. | 22 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | 1 participant received commercial drug | 0 | 1 | 0 | 0 |
| Overall Study | Adverse Event | 5 | 8 | 4 | 2 |
| Overall Study | Death | 2 | 1 | 2 | 0 |
| Overall Study | Lack of Efficacy | 6 | 6 | 7 | 9 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Missing | 2 | 0 | 0 | 2 |
| Overall Study | Other | 4 | 3 | 6 | 4 |
| Overall Study | Withdrawal by Subject | 3 | 3 | 3 | 4 |
Baseline characteristics
| Characteristic | Pomalidomide 2 mg | Prednisone | Total | Pomalidomide 0.5 mg + Prednisone | Pomalidomide 2 mg + Prednisone |
|---|---|---|---|---|---|
| Age, Continuous | 68.0 years | 66.0 years | 67.5 years | 69.5 years | 67.5 years |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0 | 11 participants | 12 participants | 43 participants | 14 participants | 6 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1 | 9 participants | 8 participants | 33 participants | 6 participants | 10 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 2 | 2 participants | 2 participants | 11 participants | 2 participants | 5 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Missing | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Janus kinase 2 (JAK2) Mutation Missing | 4 participants | 3 participants | 16 participants | 5 participants | 4 participants |
| Janus kinase 2 (JAK2) Mutation Negative | 7 participants | 6 participants | 29 participants | 8 participants | 8 participants |
| Janus kinase 2 (JAK2) Mutation Positive | 11 participants | 13 participants | 43 participants | 9 participants | 10 participants |
| Myelofibrosis with myeloid metaplasia Subtype Agnogenic Myeloid Metaplasia (AMM) | 16 participants | 16 participants | 61 participants | 13 participants | 16 participants |
| Myelofibrosis with myeloid metaplasia Subtype Postpolycythemic Myeloid Metaplasia (PPMM) | 4 participants | 3 participants | 13 participants | 2 participants | 4 participants |
| Myelofibrosis with myeloid metaplasia Subtype Postthromocythemic Myeloid Metaplasia (PTMM) | 2 participants | 3 participants | 14 participants | 7 participants | 2 participants |
| Race/Ethnicity, Customized Black | 0 participants | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Hispanic | 0 participants | 1 participants | 1 participants | 0 participants | 0 participants |
| Race/Ethnicity, Customized White | 22 participants | 21 participants | 86 participants | 22 participants | 21 participants |
| RBC Transfusion Burden | 1.0 units/28 days | 2.0 units/28 days | 1.0 units/28 days | 2.0 units/28 days | 0.0 units/28 days |
| Red Blood Cell (RBC) Transfusion Dependence No | 12 participants | 10 participants | 45 participants | 10 participants | 13 participants |
| Red Blood Cell (RBC) Transfusion Dependence Yes | 10 participants | 12 participants | 43 participants | 12 participants | 9 participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 29 Participants | 9 Participants | 7 Participants |
| Sex: Female, Male Male | 17 Participants | 14 Participants | 59 Participants | 13 Participants | 15 Participants |
| Time Since Myelofibrosis Diagnosis | 0.6 years | 1.5 years | 1.1 years | 1.7 years | 1.1 years |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 22 | 20 / 22 | 17 / 19 | 21 / 22 |
| serious Total, serious adverse events | 6 / 22 | 10 / 22 | 11 / 19 | 9 / 22 |
Outcome results
Primary
Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment
A clinical responder was defined as either: 1. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or 2. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or 3. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at \> 5 cm and became not palpable. Participants who discontinued the study early without achieving clinical response were counted as non-responders.
Time frame: Up to 168 days
Population: Modified intent-to-treat (MITT), defined as the patients who had a confirmed diagnosis of Myelofibrosis with myeloid metaplasia (MMM), received at least one dose of study drug, and participated in the study for at least 56 days.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone | Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment | 55.0 percentage of participants |
| Pomalidomide 2 mg | Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment | 23.5 percentage of participants |
| Pomalidomide 2 mg + Prednisone | Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment | 21.1 percentage of participants |
| Pomalidomide 0.5 mg + Prednisone | Percentage of Participants With a Clinical Response Within the First 6 Cycles of Treatment | 47.6 percentage of participants |
p-value: 0.092Fisher Exact
p-value: 0.048Fisher Exact
p-value: 0.758Fisher Exact
Secondary
Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores
The FACT-An comprises the four subscales of the 27-item FACT-General Scale (FACT-G), Physical Well-being, Social/Family Well-being, Emotion Well-being, Functional Well-Being, and the Additional Concerns Anemia subscale. Questions are rated on a scale from 0 to 4, where higher scores indicate more impact on quality of life. * Physical Well-being consists of 7 questions, the subscale score ranges from 0-28; * Social/Family Well-being consists of 7 questions, the subscale score ranges from 0-28; * Emotion Well-being consists of 6 questions, the subscale score ranges from 0-24; * Functional Well-Being consists of 7 questions, the subscale score ranges from 0-28; * Anemia subscale consists of 20 questions, the subscale score ranges from 0-80; * Total FACT-An score ranges from 0-188.
Time frame: Baseline and Cycle 6 (168 days).
Population: Intent-to-treat patients with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Anemia subscale | 1.2 units on a scale | Standard Deviation 9.47 |
| Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Emotional Well-Being subscale | 1.3 units on a scale | Standard Deviation 3.32 |
| Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Total FACT-An score | 2.3 units on a scale | Standard Deviation 12.42 |
| Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Functional Well-Being subscale | 0.9 units on a scale | Standard Deviation 4.14 |
| Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Social/Family Well-Being subscale | 1.9 units on a scale | Standard Deviation 3.08 |
| Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Physical Well-Being subscale | 0.6 units on a scale | Standard Deviation 1.5 |
| Pomalidomide 2 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Total FACT-An score | 1.6 units on a scale | Standard Deviation 36.51 |
| Pomalidomide 2 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Physical Well-Being subscale | 0.4 units on a scale | Standard Deviation 6.42 |
| Pomalidomide 2 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Social/Family Well-Being subscale | -1.9 units on a scale | Standard Deviation 2.59 |
| Pomalidomide 2 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Emotional Well-Being subscale | 0.0 units on a scale | Standard Deviation 4.76 |
| Pomalidomide 2 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Functional Well-Being subscale | -2.1 units on a scale | Standard Deviation 8.99 |
| Pomalidomide 2 mg | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Anemia subscale | 2.3 units on a scale | Standard Deviation 21.34 |
| Pomalidomide 2 mg + Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Social/Family Well-Being subscale | 1.7 units on a scale | Standard Deviation 3.79 |
| Pomalidomide 2 mg + Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Total FACT-An score | 27.3 units on a scale | Standard Deviation 25.74 |
| Pomalidomide 2 mg + Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Physical Well-Being subscale | 5.3 units on a scale | Standard Deviation 4.04 |
| Pomalidomide 2 mg + Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Anemia subscale | 19.3 units on a scale | Standard Deviation 18.93 |
| Pomalidomide 2 mg + Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Functional Well-Being subscale | 2.7 units on a scale | Standard Deviation 3.06 |
| Pomalidomide 2 mg + Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Emotional Well-Being subscale | -0.3 units on a scale | Standard Deviation 0.58 |
| Pomalidomide 0.5 mg + Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Physical Well-Being subscale | 2.3 units on a scale | Standard Deviation 2.26 |
| Pomalidomide 0.5 mg + Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Anemia subscale | 5.8 units on a scale | Standard Deviation 8.85 |
| Pomalidomide 0.5 mg + Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Functional Well-Being subscale | 2.5 units on a scale | Standard Deviation 6.5 |
| Pomalidomide 0.5 mg + Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Total FACT-An score | 11.4 units on a scale | Standard Deviation 13.51 |
| Pomalidomide 0.5 mg + Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Social/Family Well-Being subscale | 0.9 units on a scale | Standard Deviation 6.84 |
| Pomalidomide 0.5 mg + Prednisone | Change From Baseline in Functional Assessment of Cancer Therapy-Anemia (FACT-An) Subscale and Total Scores | Emotional Well-Being subscale | 1.7 units on a scale | Standard Deviation 3.47 |
Secondary
Change From Baseline in Hemoglobin Concentration for Non-Responders
Change from Baseline in hemoglobin for participants without a clinical response within the first 6 cycles of treatment.
Time frame: Baseline, Cycle 6 (168 days)
Population: Intent-to-treat participants with no clinical response and available hemoglobin values at each time point.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prednisone | Change From Baseline in Hemoglobin Concentration for Non-Responders | 1.2 g/dL |
| Pomalidomide 2 mg | Change From Baseline in Hemoglobin Concentration for Non-Responders | 0.1 g/dL |
| Pomalidomide 2 mg + Prednisone | Change From Baseline in Hemoglobin Concentration for Non-Responders | -0.8 g/dL |
| Pomalidomide 0.5 mg + Prednisone | Change From Baseline in Hemoglobin Concentration for Non-Responders | 0.5 g/dL |
Secondary
Change From Baseline in Hemoglobin Concentration for Responders
Change from Baseline in hemoglobin for participants with a clinical response within the first 6 cycles of treatment.
Time frame: Baseline, Cycle 6 (168 days)
Population: Intent-to-treat participants with a clinical response and available hemoglobin values at each time point.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prednisone | Change From Baseline in Hemoglobin Concentration for Responders | 1.4 g/dL |
| Pomalidomide 2 mg | Change From Baseline in Hemoglobin Concentration for Responders | 2.0 g/dL |
| Pomalidomide 0.5 mg + Prednisone | Change From Baseline in Hemoglobin Concentration for Responders | -0.1 g/dL |
Secondary
Change From Baseline in Likert Abdominal Pain Scale
Participants rated abdominal discomfort or pain over the previous week on a scale from zero to ten, where zero is no discomfort or pain and ten is the worst pain imaginable.
Time frame: Baseline and Cycle 6 (168 days)
Population: Intent-to-treat patients with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Prednisone | Change From Baseline in Likert Abdominal Pain Scale | 0.3 units on a scale | Standard Deviation 1.83 |
| Pomalidomide 2 mg | Change From Baseline in Likert Abdominal Pain Scale | -1.0 units on a scale | Standard Deviation 3.11 |
| Pomalidomide 2 mg + Prednisone | Change From Baseline in Likert Abdominal Pain Scale | 0.3 units on a scale | Standard Deviation 1.15 |
| Pomalidomide 0.5 mg + Prednisone | Change From Baseline in Likert Abdominal Pain Scale | -0.1 units on a scale | Standard Deviation 1.68 |
Secondary
Duration of First Clinical Response
For RBC-transfusion-dependent patients, duration of response was calculated as the last day of response - first day of response +1, where the last day of response was the date of the first RBC-transfusion administrated at or more than 56 days after the response started. For patients who did not receive a subsequent transfusion after the response started, the end date of response was censored at the day of last hemoglobin assessment. For RBC-transfusion-independent patients, the duration of response was calculated as the last day of response - first day of response +1, where the last day of response was the earlier of the date of a hemoglobin increase of \< 2.0 g/dL and the date of a RBC transfusion at ≥ 56 days after the response started. For patients whose hemoglobin measurements were always ≥ 2.0 g/dL and never received a RBC transfusion after response started, the end date of the response was censored at the date of last hemoglobin measurement. Kaplan-Meier methodology was used.
Time frame: Up to 40 months
Population: Intent-to-treat population with a clinical response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prednisone | Duration of First Clinical Response | 3.7 months |
| Pomalidomide 2 mg | Duration of First Clinical Response | NA months |
| Pomalidomide 2 mg + Prednisone | Duration of First Clinical Response | 6.0 months |
| Pomalidomide 0.5 mg + Prednisone | Duration of First Clinical Response | 10.6 months |
Secondary
Number of Participants With Adverse Events (AEs)
A serious AE (SAE) was defined as any AE which resulted in death or was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or constituted an important medical event (events that may have jeopardized the patient or required intervention to prevent one of the outcomes listed above). The severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) or according to the following scale: Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Death. The Investigator determined the relationship between study drug and the occurrence of an AE as Not Related or Related (since the study was double-blinded, a patient receiving only prednisone could have an AE that was judged as related to pomalidomide, and vice-versa).
Time frame: From date of the first dose of the study drug until discontinuation or the data cut-off date (up to approximately 45 months).
Population: Safety population (all treated patients).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Prednisone | Number of Participants With Adverse Events (AEs) | At least one SAE related to pomalidomide | 4 participants |
| Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of prednisone | 5 participants |
| Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to a dose interruption of prednisone | 2 participants |
| Prednisone | Number of Participants With Adverse Events (AEs) | At least one SAE related to prednisone | 4 participants |
| Prednisone | Number of Participants With Adverse Events (AEs) | At least one AE related to prednisone | 10 participants |
| Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of pomalidomide | 7 participants |
| Prednisone | Number of Participants With Adverse Events (AEs) | At least one Grade 3-4 AE | 10 participants |
| Prednisone | Number of Participants With Adverse Events (AEs) | At least one AE related to pomalidomide | 15 participants |
| Prednisone | Number of Participants With Adverse Events (AEs) | At least one Grade 3-4 AE related to pomalidomide | 6 participants |
| Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to a dose interruption of pomalidomide | 5 participants |
| Prednisone | Number of Participants With Adverse Events (AEs) | At least one Grade 3-4 AE related to prednisone | 5 participants |
| Prednisone | Number of Participants With Adverse Events (AEs) | At least one AE | 20 participants |
| Prednisone | Number of Participants With Adverse Events (AEs) | At least one SAE | 6 participants |
| Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to a dose reduction of pomalidomide | 0 participants |
| Pomalidomide 2 mg | Number of Participants With Adverse Events (AEs) | At least one AE | 21 participants |
| Pomalidomide 2 mg | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of prednisone | 7 participants |
| Pomalidomide 2 mg | Number of Participants With Adverse Events (AEs) | AE leading to a dose reduction of pomalidomide | 2 participants |
| Pomalidomide 2 mg | Number of Participants With Adverse Events (AEs) | At least one Grade 3-4 AE related to pomalidomide | 7 participants |
| Pomalidomide 2 mg | Number of Participants With Adverse Events (AEs) | At least one AE related to pomalidomide | 17 participants |
| Pomalidomide 2 mg | Number of Participants With Adverse Events (AEs) | At least one SAE related to prednisone | 3 participants |
| Pomalidomide 2 mg | Number of Participants With Adverse Events (AEs) | At least one SAE related to pomalidomide | 6 participants |
| Pomalidomide 2 mg | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of pomalidomide | 11 participants |
| Pomalidomide 2 mg | Number of Participants With Adverse Events (AEs) | At least one SAE | 10 participants |
| Pomalidomide 2 mg | Number of Participants With Adverse Events (AEs) | At least one AE related to prednisone | 10 participants |
| Pomalidomide 2 mg | Number of Participants With Adverse Events (AEs) | AE leading to a dose interruption of prednisone | 8 participants |
| Pomalidomide 2 mg | Number of Participants With Adverse Events (AEs) | AE leading to a dose interruption of pomalidomide | 9 participants |
| Pomalidomide 2 mg | Number of Participants With Adverse Events (AEs) | At least one Grade 3-4 AE related to prednisone | 2 participants |
| Pomalidomide 2 mg | Number of Participants With Adverse Events (AEs) | At least one Grade 3-4 AE | 14 participants |
| Pomalidomide 2 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one Grade 3-4 AE related to prednisone | 6 participants |
| Pomalidomide 2 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one AE | 18 participants |
| Pomalidomide 2 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one AE related to pomalidomide | 16 participants |
| Pomalidomide 2 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one AE related to prednisone | 11 participants |
| Pomalidomide 2 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one Grade 3-4 AE | 13 participants |
| Pomalidomide 2 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one Grade 3-4 AE related to pomalidomide | 11 participants |
| Pomalidomide 2 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one SAE | 11 participants |
| Pomalidomide 2 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one SAE related to pomalidomide | 8 participants |
| Pomalidomide 2 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one SAE related to prednisone | 5 participants |
| Pomalidomide 2 mg + Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of pomalidomide | 5 participants |
| Pomalidomide 2 mg + Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of prednisone | 2 participants |
| Pomalidomide 2 mg + Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to a dose reduction of pomalidomide | 1 participants |
| Pomalidomide 2 mg + Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to a dose interruption of pomalidomide | 9 participants |
| Pomalidomide 2 mg + Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to a dose interruption of prednisone | 6 participants |
| Pomalidomide 0.5 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one AE related to pomalidomide | 15 participants |
| Pomalidomide 0.5 mg + Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of prednisone | 1 participants |
| Pomalidomide 0.5 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one SAE | 8 participants |
| Pomalidomide 0.5 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one Grade 3-4 AE related to prednisone | 3 participants |
| Pomalidomide 0.5 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one AE | 21 participants |
| Pomalidomide 0.5 mg + Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to a dose reduction of pomalidomide | 1 participants |
| Pomalidomide 0.5 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one Grade 3-4 AE related to pomalidomide | 6 participants |
| Pomalidomide 0.5 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one AE related to prednisone | 5 participants |
| Pomalidomide 0.5 mg + Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to a dose interruption of prednisone | 3 participants |
| Pomalidomide 0.5 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one SAE related to prednisone | 3 participants |
| Pomalidomide 0.5 mg + Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to a dose interruption of pomalidomide | 7 participants |
| Pomalidomide 0.5 mg + Prednisone | Number of Participants With Adverse Events (AEs) | AE leading to discontinuation of pomalidomide | 6 participants |
| Pomalidomide 0.5 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one Grade 3-4 AE | 15 participants |
| Pomalidomide 0.5 mg + Prednisone | Number of Participants With Adverse Events (AEs) | At least one SAE related to pomalidomide | 3 participants |
Secondary
Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment
A clinical responder was defined as either: 1. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or 2. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or 3. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at \> 5 cm and became not palpable. Participants who discontinued the study early without achieving clinical response were counted as non-responders.
Time frame: Up to 336 days
Population: Intent-to-treat (ITT), defined as as all patients who were randomized, independent of whether they received study treatment or not.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone | Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment | 50.0 percentage of participants |
| Pomalidomide 2 mg | Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment | 18.2 percentage of participants |
| Pomalidomide 2 mg + Prednisone | Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment | 18.2 percentage of participants |
| Pomalidomide 0.5 mg + Prednisone | Percentage of Participants With a Clinical Response Within the First 12 Cycles of Treatment | 45.5 percentage of participants |
Secondary
Percentage of Participants With Clinical Response by Baseline JAK2 Assessment
Percentage of participants who achieved a clinical response, presented by participants with positive and negative janus kinase 2 (JAK2) V617F mutation results at Baseline.
Time frame: Up to 336 days
Population: Intent-to-treat population with non-missing JAK2 Baseline assessment results. The number of participants analyzed indicates the number of participants with a positive or negative JAK2 result for each treatment group respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisone | Percentage of Participants With Clinical Response by Baseline JAK2 Assessment | 46.2 percentage of participants |
| Pomalidomide 2 mg | Percentage of Participants With Clinical Response by Baseline JAK2 Assessment | 27.3 percentage of participants |
| Pomalidomide 2 mg + Prednisone | Percentage of Participants With Clinical Response by Baseline JAK2 Assessment | 30.0 percentage of participants |
| Pomalidomide 0.5 mg + Prednisone | Percentage of Participants With Clinical Response by Baseline JAK2 Assessment | 66.7 percentage of participants |
| Prednisone, Negative JAK2 | Percentage of Participants With Clinical Response by Baseline JAK2 Assessment | 50.0 percentage of participants |
| Pomalidomide 2 mg, Negative JAK2 | Percentage of Participants With Clinical Response by Baseline JAK2 Assessment | 28.6 percentage of participants |
| Pomalidomide 2 mg + Prednisone, Negative JAK2 | Percentage of Participants With Clinical Response by Baseline JAK2 Assessment | 12.5 percentage of participants |
| Pomalidomide 0.5 mg + Prednisone, Negative JAK2 | Percentage of Participants With Clinical Response by Baseline JAK2 Assessment | 25.0 percentage of participants |
Secondary
Time to the First Clinical Response
The time to the first clinical response achieved within 168 days after the first study drug dosing date was calculated for participants who achieved a clinical response as: Start date of the first clinical response - the first study drug date +1. A clinical responder was defined as either: 1. A baseline red blood cell (RBC)-transfusion-dependent participant with a ≥ 56 consecutive day RBC transfusion-free period after the first dose of study drug, or 2. A baseline RBC-transfusion-independent participant with an increase in hemoglobin of 2.0 g/dL or more from baseline for ≥ 56 consecutive days in the absence of RBC transfusions, or 3. A participant with either a ≥ 50% reduction in palpable splenomegaly of a spleen that was ≥ 10 cm at baseline or a spleen that was palpable at \> 5 cm and became not palpable.
Time frame: Up to 168 days
Population: Intent-to-treat population with a clinical response
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Prednisone | Time to the First Clinical Response | 0.3 weeks |
| Pomalidomide 2 mg | Time to the First Clinical Response | 8.0 weeks |
| Pomalidomide 2 mg + Prednisone | Time to the First Clinical Response | 10.1 weeks |
| Pomalidomide 0.5 mg + Prednisone | Time to the First Clinical Response | 1.2 weeks |