Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Pomalidomide · 20 trials · 15 indications
Progression free survival (PFS) will be calculated as the time between the randomization and progressive disease (PD) or death. Progressive Disease is defined as an Increase of ≥ 25% from nadir in: * Serum M-component and/or (the absolute increase must be ≥ 0.5 g/dL)g * Urine M-component and/or (the absolute increase must be ≥ 200 mg/24 hours) * In patients without measurable serum and urine M-protein levels the difference between involved and uninvolved FLC levels, the absolute increase must be \> 100 mg/dL. * Bone marrow plasma cell percentage, the absolute % must be ≥ 10%h * Definite development of new bone lesions or soft tissue plasmacytomas increase in the size of existing bone lesions or soft tissue plasmacytomas. -Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder.
An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, regardless of etiology. Any worsening (i.e., any significant adverse change in the frequency or intensity of a pre- existing condition) was considered an AE. The severity of AEs were graded based on the symptoms according to version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events. Second primary malignancies were monitored as events of interest and considered as part of the assessment of AEs. A SAE = AE occurring at any dose that: * Results in death; * Is life-threatening * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect
Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease required 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.
Progression-free survival was calculated as the time from randomization to disease progression as determined by the Independent Response Adjudication Committee based on the International Myeloma Working Group Uniform Response criteria (IMWG), or death on study, whichever occurred earlier. Progressive disease requires 1 of the following: • Increase of ≥ 25% from nadir in: o Serum M-component (absolute increase ≥ 0.5 g/dl); o Urine M-component (absolute increase ≥ 200 mg/24 hours); o Bone marrow plasma cell percentage (absolute % ≥ 10%); • Development of new or increase in the size of existing bone lesions or soft tissue plasmacytomas; • Development of hypercalcemia (corrected serum calcium \> 11.5 mg/dl) attributed solely to plasma cell proliferative disease.
Objective response defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) based on Investigator Assessment. SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-protein and urine M-protein level \<100 mg/24 hours; PR: ≥50% reduction of serum M-Protein and reduction in urinary M-protein by ≥90% or to \<200 mg/24 hours. A ≥50% decrease in the difference between involved and uninvolved FLC levels in place of the M-protein criteria or a ≥50% reduction in plasma cells in place of M-protein if baseline was ≥30%. If present at baseline a ≥50% reduction in size of soft tissue plasmacytomas.
RBC-transfusion independence was defined as the absence of RBC transfusions for any consecutive 84-day interval.
A response in the China extension study was defined as an increase in hemoglobin ≥ 15 g/L above baseline value (in the absence of RBC transfusion) for ≥ 84 consecutive days.
The percentage of participants who achieved either an objective response, defined as a complete response (CR) or partial response (PR) in the first 6 cycles of treatment (or within 3 cycles for DIPG), or long-term stable disease (SD) defined as SD maintained for ≥ 6 cycles (≥ 3 cycles for DIPG), measured from first dose date. CR: Disappearance of all lesions and no new lesions. PR: A reduction of ≥ 50% in the size of measurable lesions, and/or persistence of non-target lesions with no progression or decrease in size. SD: A decrease of \< 50% or an increase of \< 25% in the size of measurable lesions and no evidence of new lesions, response does not meet the criteria for CR, PR, or progressive disease, and/or the persistence of non-target lesions with no progression or decrease in size. Progressive Disease (PD): ≥ 25% increase in the size of the measurable lesions, or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
ORR per Modified International Myeloma Working Group (mIMWG) Criteria is defined as the percentage of participants who achieve best overall response of Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR). CR=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow VGPR=Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine Mprotein level \< 100 mg per 24 hours PR=≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by ≥ 90% or to \< 200 mg per 24 hours
Overall response rate determined by Myeloma responses determined by modified IMWG criteria
Myeloma response was defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.
Myeloma response was defined as a best overall response of stringent complete response (SCR), complete response (CR), very good partial response (VGPR) or partial response (PR) SCR: CR and normal free light chain (FLC) ratio and no clonal cells in bone marrow; CR: Negative serum and urine on immunofixation, disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or ≥ 90% reduction in serum M-protein and urine M-protein level \< 100 mg/24 hours; PR: ≥ 50% reduction of serum M-Protein and reduction in urinary M-protein by ≥ 90% or to \< 200 mg/24 hours. In addition to the above, if present at baseline a ≥ 50% reduction in the size of soft tissue plasmacytomas is also required.
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.
Maximum observed concentration in plasma
Time to maximum observed concentration in plasma
Area under the plasma concentration-time curve
Terminal half-life
Apparent volume of distribution
Apparent total body clearance
To evaluate the effect of pomalidomide on the time matched changes from placebo in the baseline adjusted QT interval of the electrocardiogram (ECG) using the Fridericia correction method (QTcF)
Observed maximum concentration; PK parameter for plasma pomalidomide
Time to Cmax
Area under the plasma concentration-time curve from time zero to time t, where t is the last measurable time point
Area under the plasma concentration-time curve from time zero extrapolated to infinity; PK parameter for plasma pomalidomide
Estimate of the terminal elimination half-life in plasma 5. delay between time of administration and absorption
Apparent total plasma or serum clearance of drug after oral administration
Apparent volume of distribution during terminal phase after oral / extravascular administration
Cmax-Maximum observed concentration in plasma
Tmax: Time to maximum concentration
AUC-Area under the plasma concentration-time curve
T1/2-Terminal half-life
CL/F-Apparent total plasma clearance
Vz/F: Apparent total volume of distribution
To determine the maximum tolerated dose (MTD)
The maximum tolerated dose was defined as the highest dose level at which no more than 1 of 6 participants experiences a DLT within the first 28-day cycle. DLTs were defined as: * Grade 4 neutropenia or thrombocytopenia * Febrile neutropenia * Grade 3 or 4 nausea, vomiting or diarrhea despite optimal symptomatic treatment * Serum transaminase \> 20 \* upper limit of normal (ULN) * Serum transaminase \> 5 \* ULN for \>= 7 days * Delay of the start of cycle 2 by \>7 days due to pomalidomide-related adverse event
Progression free survival (PFS) is the time from randomization to the first documentation of disease progression or death from any cause during study, whichever occurs earlier. Disease progression was assessed by the Independent Response Adjudication Committee (IRAC). For the primary PFS analysis, participants who withdrew for any reason or received another antimyeloma therapy (except adding dexamethasone to the Phase 2: Pomalidomide arm) without documented PD (as determined by the IRAC review) were censored on the date of their last adequate response assessment, prior to receiving any other anti-myeloma therapy. Subjects who were still active at the time of the data cut-off date without PD (as determined by the IRAC) were censored on the date of their last adequate response assessment. Data collection is ongoing and future data results will be included as available.
Percentage of participants with the progression-free survival events: disease progression and death. Disease progression was assessed by the Independent Response Adjudication Committee (IRAC). Data collection is ongoing and future data results will be included as available.
Maximum Tolerated Dose
| Arm | Type | Description |
|---|---|---|
| Pomalidomide, Bortezomib and Low Dose Dexamethasone | EXPERIMENTAL | 4 mg of Pomalidomide will be taken orally on Days 1-14 of a 21-day cycle along with 1.3 mg/m2 of Bortezomib administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on days 1, 8 of 21 days for cycle 9 and onward until disease progression, and Dexamethasone 20 mg/day \[≤ 75 years old\] or 10 mg/day \[\> 75 years old\] orally on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on days 1, 2,8, 9 of 21 days for cycles 9 and onward until disease progression. |
| Bortezomib and Low Dose Dexamethasone | ACTIVE_COMPARATOR | 1.3 mg/m2 of Bortezomib will be administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on Days 1, 8 of 21 days for cycle 9 and onward until disease progression along with Dexamethasone 20 mg/day \[≤ 75 years old\]or 10 mg/day \[\> 75 years old\] orally on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on Days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression. |
| Pomalidomide plus Dexamethasone | EXPERIMENTAL | Pomalidomide 4mg by mouth (PO) daily days 1 through 21 of a 28 day cycle and dexamethasone 40mg/day PO for those ≤75 years of age or 20mg/day for those greater than 75 years of age on Days 1, 8, 15 and 22 of a 28 day cycle. |
| Pomalidomide + Low-Dose Dexamethasone | EXPERIMENTAL | Participants received 4 mg pomalidomide administered by mouth on Days 1 to 21 of each 28-day treatment cycle and 40 mg dexamethasone (or 20 mg for participants \> 75 years of age) administered by mouth once per day on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression. |
| High-Dose Dexamethasone | ACTIVE_COMPARATOR | Participants received 40 mg dexamethasone (or 20 mg for participants \> 75 years of age) administered by mouth once per day on Days 1 to 4, 9 to 12, and 17 to 20 of each 28-day treatment cycle until disease progression. |
| Pomalidomide | EXPERIMENTAL | Oral pomalidomide 4 mg on Days 1-21 of 28-day cycle until progressive disease (PD) or unacceptable toxicity |
| Pomalidomide 0.5 mg | EXPERIMENTAL | Participants received pomalidomide 0.5 mg/day by mouth for at least 168 days unless there were unacceptable side effects or disease progression. Participants who were RBC-transfusion independent or experienced clinical benefit (defined as a reduction from Baseline of ≥ 50% in RBC-transfusion frequency during the prior 84-day interval) could continue to receive pomalidomide until loss of RBC-transfusion independence response or clinical benefit, or other criteria for treatment discontinuation applied. |
| Placebo | PLACEBO_COMPARATOR | Participants received placebo taken by mouth once daily for at least 168 days unless there were unacceptable side effects or disease progression. Participants who were RBC-transfusion independent or experienced clinical benefit could continue to receive placebo until loss of RBC- transfusion independence response or clinical benefit, or other criteria for treatment discontinuation applied. |
| China Extension: Pomalidomide 0.5 mg | EXPERIMENTAL | Participants received pomalidomide 0.5 mg/day by mouth for at least 168 days unless there were unacceptable side effects, disease progression, or they received a RBC-transfusion. Participants who experienced anemia response could continue treatment until the response was lost or other criteria for treatment discontinuation applied. |
| Pomalidomide + dexamethasone | EXPERIMENTAL | Each subject enrolled in the study will take oral pomalidomide (4 mg) once daily on Days 1-21 and dexamethasone 40 mg/day (\< 75 years old) or 20 mg/day (\>75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle. |
| Pomalidomide + Dexamethasone + Daratumumab | EXPERIMENTAL | Each subject enrolled in the study will take oral pomalidomide (4 mg) once daily on Days 1-21 and dexamethasone 40 mg/day (\< 75 years old) or 20 mg/ day (\>75 years old) on Days 1, 8, 15 and 22 of a 28-day cycle and daratumumab administered intravenously (IV) at a starting dose of 16 mg/kg at following schedule: * Days 1, 8, 15, and 22 of a 28-day cycle for Cycle 1 and Cycle 2 * Days 1 and 15 for Cycle 3 through Cycle 6 * Day 1 for Cycle 7 and each cycle thereafter until disease progression |
| Pomalidomide and low dose Dexamethasone | EXPERIMENTAL | Pomalidomide 4mg, and low dose Dexamethasone, starting at 40mgs(≤ 75 years old) or 20 mg/day (\> 75 years old) |
| Prednisone | EXPERIMENTAL | 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. |
| Pomalidomide 2 mg + Prednisone | EXPERIMENTAL | 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, participants 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, were eligible to participate in the extension phase and continue to receive oral pomalidomide 2 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal. |
| Pomalidomide 0.5 mg + Prednisone | EXPERIMENTAL | 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, participants 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, were eligible to participate in the extension phase and continue to receive oral pomalidomide 0.5 mg daily, from Days 1-28 of each cycle, until disease progression, unacceptable toxicity or voluntary withdrawal. |
| Single Group Assignment | EXPERIMENTAL | Combination Pomalidomide, low-dose Dexamethasone, and Marizomib: |
| 4 mg Pomalidomide - Fed | EXPERIMENTAL | On Day 1, participants will receive a single oral dose of 4 mg pomalidomide under fed conditions. |
| 4 mg Pomalidomide - Fasted | EXPERIMENTAL | On Day 1, participants will receive a single oral dose of 4 mg pomalidomide under fasted conditions |
| 4 mg Pomalidomide + caffeine - Non-smoking | EXPERIMENTAL | Participants will remain in the clinical site for a total of 10 days. They will receive orally a 200-mg caffeine capsule on Day 6, and on Day 8, participants will receive a single oral dose of 4 mg pomalidomide. |
| 4 mg Pomalidomide + caffeine - Smoking | EXPERIMENTAL | Participants will be required to smoke approximately 20 cigarettes a day for 10 days. They will receive orally a 200-mg caffeine capsule on Day 6, and on Day 8, participants will receive a single oral dose of 4 mg pomalidomide. |
| Treatment 1 (placebo) | PLACEBO_COMPARATOR | Five placebo capsules matching the appearance of the 4 mg pomalidomide capsule will be administered orally on the morning of Day 1 |
| Treatment 2 (4 mg pomalidomide) | EXPERIMENTAL | Five capsules (one 4 mg pomalidomide capsule and four placebo capsules matching the appearance of the 4 mg pomalidomide capsule) will be administered orally on the morning of Day 1 |
| Treatment 3 (20 mg pomalidomide) | EXPERIMENTAL | Five 4 mg pomalidomide capsules will be administered orally on the morning of Day 1 |
| Treatment 4 (moxifloxacin) | ACTIVE_COMPARATOR | One 400 mg moxifloxacin tablet (AVELOX®, moxifloxacin hydrochloride, Bayer Pharmaceuticals Corporation) will be administered orally on the morning of Day 1 |
| Part 1: Severe liver disease and healthy volunteer match | EXPERIMENTAL | Subjects with severe liver disease (Group 2) and healthy volunteer subjects (Group 1) matched to the subjects with liver disease |
| Part 2: Mild and moderate Liver disease | EXPERIMENTAL | Subjects with moderate (Group 3) and/or mild (Group 4) liver disease |
| Pomalidomide plus Ketoconazole | EXPERIMENTAL | - |
| Pomalidomide plus Ketoconazole plus Fluvoxamine | EXPERIMENTAL | - |
| Pomalidomide plus Carbamazepine | EXPERIMENTAL | - |
| Pomalidomide/Bortezomib/Dexamethasone | EXPERIMENTAL | 1, 2, 3 or 4 mg of pomalidomide will be taken orally on Days 1-14 of a 21-day cycle along with 1 or 1.3 mg/m2 of bortezomib administered intravenously or subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on days 1, 8 of 21 days for cycle 9 and onward until disease progression, and dexamethasone 20 mg/day \[≤ 75 years old\] or 10 mg/day \[\> 75 years old\] orally on days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression |
| 0.5-mg Pomalidomide or placebo (Cohort A) | EXPERIMENTAL | A single 0.5-mg pomalidomide capsule or matching placebo administered once daily for 5 days under fasted conditions |
| 1-mg Pomalidomide or placebo (Cohort B) | EXPERIMENTAL | This arm may be initiated pending a safety review of Cohort A. A single 1-mg pomalidomide capsule or matching placebo administered once daily for 5 days under fasted conditions. |
| 2-mg Pomalidomide or placebo (Cohort C) | EXPERIMENTAL | This arm may be initiated pending a safety review of Cohort B. A single 2-mg pomalidomide capsule or matching placebo administered once daily for 5 days under fasted conditions. |
| Phase 1: 2 mg pomalidomide | EXPERIMENTAL | Pomalidomide 2 mg daily on days 1-21 of each 28-day cycle. Participants with progressive disease (PD) had the option of adding dexamethasone 40 mg on Days 1, 8, 15, 22 of each 28-day cycle to the pomalidomide treatment, or discontinuing study treatment. |
| Phase 1: 3 mg pomalidomide | EXPERIMENTAL | Pomalidomide 3 mg daily on days 1-21 of each 28-day cycle. Participants with progressive disease (PD) had the option of adding dexamethasone 40 mg on Days 1, 8, 15, 22 of each 28-day cycle to the pomalidomide treatment, or discontinuing study treatment. |
| Phase 1: 4 mg pomalidomide | EXPERIMENTAL | Pomalidomide 4 mg daily on days 1-21 of each 28-day cycle. Participants with progressive disease (PD) had the option of adding dexamethasone 40 mg on Days 1, 8, 15, 22 of each 28-day cycle to the pomalidomide treatment, or discontinuing study treatment. |
| Phase 1: 5 mg pomalidomide | EXPERIMENTAL | Pomalidomide 5 mg daily on days 1-21 of each 28-day cycle. Participants with progressive disease (PD) had the option of adding dexamethasone 40 mg on Days 1, 8, 15, 22 of each 28-day cycle to the pomalidomide treatment, or discontinuing study treatment. |
| Phase 2: pomalidomide + dexamethasone | EXPERIMENTAL | Combination therapy of 4 mg pomalidomide given once per day on Days 1-21 of each 28-day cycle and the starting dose of dexamethasone (determined by age) on days 1, 8, 15, and 22 of each 28-day cycle. The starting dose of dexamethasone was 40 mg for participants who were ≤ 75 years of age and 20 mg for participants who were \> 75 years of age. Dose reduction steps for dexamethasone were provided for drug-related toxicities. |
| Phase 2: pomalidomide | EXPERIMENTAL | 4 mg pomalidomide was given once per day on Days 1-21 of each 28-day cycle until PD. Participants in the single agent pomalidomide treatment arm who developed confirmed PD at any time had the option to receive oral dexamethasone on days 1, 8, 15, and 22 of each 28-day cycle at the starting dose of 20 or 40 mg depending on age in addition to their current dose of pomalidomide, or to discontinue treatment. |
| Cohort 1: 0.5 mg pomalidomide | EXPERIMENTAL | 0.5 mg pomalidomide orally daily for 84 days |
| Cohort 2: 1.0 mg pomalidomide | EXPERIMENTAL | 1.0 mg pomalidomide orally daily for 84 days |
| Cohort 3: 2.0 mg pomalidomide | EXPERIMENTAL | 2.0 mg pomalidomide orally daily for 84 days |
| Cohort 4: 3.0 mg pomalidomide | EXPERIMENTAL | 3.0 mg pomalidomide orally daily for 84 days |
| Cohort 5: 4.0 mg pomalidomide | EXPERIMENTAL | 4.0 mg pomalidomide orally daily for 84 days |
| Name | Type | Description |
|---|---|---|
| Pomalidomide | DRUG | Pomalidomide 4 mg will be taken orally on Days 1-14 of a 21-day cycle. |
| Bortezomib | DRUG | Bortezomib 1.3 mg/m2 will be administered subcutaneously on Days 1, 4, 8 and 11 of 21 days for cycles 1 -8 and on Days 1, 8 of 21 days for cycle 9 and onward until disease progression. |
| Dexamethasone | DRUG | Dexamethasone 20 mg/day \[≤ 75 years old\] or 10 mg/day \[\>75 years old\] will be taken orally on Days 1, 2, 4, 5, 8, 9, 11, 12 of 21 days for cycles 1-8 and on Days 1, 2, 8, 9 of 21 days for cycles 9 and onward until disease progression. |
| Pomalidomide 0.5 mg | DRUG | Pomalidomide 0.5 mg capsule taken by mouth once daily. Immunomodulatory agent with demonstrated efficacy in the treatment of subjects with RBC-transfusion-dependence associated with MNP-associated myelofibrosis. |
| Placebo | DRUG | Placebo Comparator to active drug; Placebo capsule taken by mouth once daily |
| Daratumumab | DRUG | - |
| Pomalidomide and Dexamethasone | DRUG | - |
| Prednisone | DRUG | 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. |
| Placebo to pomalidomide | DRUG | Matching pomalidomide placebo tablets |
| Placebo to prednisone | DRUG | Matching prednisone placebo tablets |
| marizomib | DRUG | IV Marizomib, 0.2 to 0.5 mg/m2 on days 1, 4, 8, 11 of 28 day cycle |
| low-dose dexamethasone | DRUG | Oral Dexamethasone, days 1, 2, 4, 5, 8, 9, 11, 12, 15, 16, 22, 23 of 28 day cycle, 5 or 10 mg |
| Caffeine | OTHER | Capsules |
| Tobacco | OTHER | Cigarettes |
| Moxifloxacin | DRUG | Single oral dose of 400 mg moxifloxacin tablet |
| Ketoconazole | DRUG | 200 mg Ketoconazole tablet administered orally twice a day on Days 1-7. |
| Fluvoxamine | DRUG | 50 mg Fluvoxamine tablet administered orally twice a day on Days 1-7. |
| Carbamazepine | DRUG | 100 mg Carbamazepine tablet administered orally once in the evening on Day 1 100 mg Carbamazepine tablet administered orally twice daily on Days 2-3 200 mg Carbamazepine tablet administered orally twice daily on Days 4-11 |
| Aspirin | DRUG | As prophylactic anti-thrombotic treatment, all participants were given aspirin 81-100 mg daily (commercial supply) unless contraindicated. If aspirin was contraindicated, participants were given another form of anti-thrombotic therapy according to hospital guidelines or physician preference. |
Inclusion Criteria: * Must be ≥ 18 years at the time of signing informed consent. * Must have documented diagnosis of multiple myeloma and have measureable disease by serum and urine protein electrophoresis. * Must have had at least 1 but no greater than 3 prior anti-myeloma regimens. * Must have d...
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Pomalidomide is an investigational small molecule being studied for multiple conditions, including multiple myeloma in relapse, myelofibrosis with myeloid metaplasia, primary myelofibrosis, sickle cell disease, and recurrent or progressive primary brain tumors in children and young adults. It is also used in healthy volunteer studies for clinical pharmacology research.
Pomalidomide is being developed by Bristol-Myers Squibb Company, traded on the New York Stock Exchange under the ticker BMY. The company is conducting clinical trials to evaluate the drug's safety and effectiveness across several oncology and non-oncology indications.
Pomalidomide is in Phase 2 clinical development. All 10 completed trials are finished, with no active trials currently enrolling. The drug remains investigational and has not been approved by the FDA for any of the studied indications.
Pomalidomide belongs to the -domide (cereblon) target class of small molecules. It works by binding to cereblon, a protein involved in ubiquitination, which leads to the degradation of specific transcription factors and modulation of immune responses.
Pomalidomide has completed 10 clinical trials with a total enrollment of 2,378 participants. Notable trials include NCT00463385 for myelofibrosis with myeloid metaplasia, NCT01522547 for sickle cell disease, NCT02168205 for healthy volunteers, and NCT03257631 for pediatric brain tumors.
Pomalidomide is a distinct investigational drug and is not known to be the same as any other approved medication. It is being studied as a monotherapy in several trials, including for children and young adults with recurrent or progressive primary brain tumors.