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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1166-8401 | Other Identifier | WHO |
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The primary objective of this study is to determine the safety profile, tolerability, and maximum tolerated dose of ixazomib citrate (MLN9708) when taken orally on a weekly dosing schedule by patients with relapsed and refractory multiple myeloma (RRMM). Secondary objectives include pharmacokinetics and response rates.
The drug being tested in this study is called ixazomib citrate (MLN9708). Ixazomib citrate is being tested for people who have multiple myeloma who have relapsed after treatment or become unresponsive to treatment.
This study will determine the maximum tolerated dose (MTD) of ixazomib citrate using a dose escalation scheme. Once MTD is established, participants will be enrolled at MTD into one of the 4 expansion cohorts to characterize the safety, tolerability and efficacy of MLN9708. Blood samples for safety labs, hematology, serum chemistry and pharmacokinetic evaluations will be obtained at the timepoints specified. Disease response assessment is to be performed on the first day of every other cycle beginning with Cycle 3.
The study will enroll approximately 60 patients. All participants will receive treatment with ixazomib citrate. This multi-center trial will be conducted in the United States. The overall time to participate in this study is up to 60 days, and participants will make 12-16 visits to the clinic for study procedures.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 0.24 mg/m^2 | Experimental | Ixazomib citrate, 0.24 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate |
|
| 0.48 mg/m^2 | Experimental | Ixazomib citrate, 0.48 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
| 0.80 mg/m^2 | Experimental | Ixazomib citrate, 0.80 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
| 1.20 mg/m^2 | Experimental | Ixazomib citrate, 1.20 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. |
|
| 1.68 mg/m^2 | Experimental | Ixazomib citrate, 1.68 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ixazomib citrate | Drug | Ixazomib citrate capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Reporting One or More Treatment-Emergent Adverse Events and Serious Adverse Events | An Adverse Event is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. | From the first dose through 30 days after last dose of ixazomib citrate or until the start of subsequent antineoplastic therapy (Up to 354 days) |
| Neurotoxicity Grading | Neurotoxicity is graded using participant responses to 11 functional questions on a 5-point scale, where 0=Not at all and 4=Very much, using the Functional Assessment of Cancer Therapy/Gynecology Oncology Group - Neurotoxicity Questionnaire, Version 4.0(14). Neurotoxicity subscale is a sum of 11 reversed item scores where each original score is transformed as (4 - score). The highest possible score is 44, and a higher score indicates more neurotoxicity. | Cycle 1 Day 1 and End of Study (Up to 354 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax: Maximum Observed Plasma Concentration for MLN2238 | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). | Days 1 and 15 of Cycle 1 |
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Inclusion Criteria:
Each patient must meet all of the following eligibility criteria to be enrolled in the study:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Monitor | Millennium Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic- Scottsdale | Scottsdale | Arizona | 85259 | United States | ||
| James R. Berenson, MD, Inc |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28803351 | Derived | Gupta N, Yang H, Hanley MJ, Zhang S, Liu R, Kumar S, Richardson PG, Skacel T, Venkatakrishnan K. Dose and Schedule Selection of the Oral Proteasome Inhibitor Ixazomib in Relapsed/Refractory Multiple Myeloma: Clinical and Model-Based Analyses. Target Oncol. 2017 Oct;12(5):643-654. doi: 10.1007/s11523-017-0524-3. | |
| 24904120 | Derived |
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Participants with a diagnosis of multiple myeloma (relapsed and/or refractory) were enrolled in the dose escalation phase to determine maximum tolerated dose (MTD). Once the MTD was established, participants were enrolled at the MTD into 1 of the 4 expansion cohorts.
Sixty (60) participants took part in the study at 6 investigative sites in the United States from 31 October 2009 to database lock on 28 February 2013.
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| ID | Title | Description |
|---|---|---|
| FG000 | 0.24 mg/m^2 | Ixazomib citrate, 0.24 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| FG001 | 0.48 mg/m^2 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Dose Escalation Phase |
|
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|
| 2.23 mg/m^2 | Experimental | Ixazomib citrate, 2.23 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
| 2.97 mg/m^2 | Experimental | Ixazomib citrate, 2.97 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
| 3.95 mg/m^2 | Experimental | Ixazomib citrate, 3.95 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
| Relapsed and Refractory (RR) | Experimental | Ixazomib citrate, 2.97 mg/m^2 established Maximum Tolerated Dose (MTD), capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
| VELCADE-Relapsed (VR) | Experimental | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
| PI naïve | Experimental | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
| Carfilzomib | Experimental | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
|
| Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for MLN2238 |
Tmax: Time to reach the maximum observed plasma concentration (Cmax), equal to time to Cmax. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). |
| Days 1 and 15 of Cycle 1 |
| AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for MLN2238 | AUC(0-168) is a measure of the area under the plasma concentration-time curve over the dosing interval (tau) (AUC[0-tau]), where tau is the length of the dosing interval - 168 hours in this study). MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). | Days 1 and 15 of Cycle 1 |
| Accumulation Ratio: Day 15 AUC0-168 / Day 1 AUC0-168 for MLN2238 | MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). | Day 15 of Cycle 1 |
| Terminal Elimination Rate Constant (λz) for MLN2238 | Terminal elimination rate constant (λz) is the rate at which drugs are eliminated from the body and the values were used for calculation of T1/2. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). | Day 15 of Cycle 1 |
| Terminal Phase Elimination Half-life (T1/2) for MLN2238 | Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). | Day 15 of Cycle 1 |
| Emax: Maximum Inhibition | A Whole Blood 20S Proteasome Inhibition Parameter. There were no subjects in the Pharmacodynamic (PD) Analysis Set for the 2.23 mg/m^2 cohort, so PD tables do not include that arm. | Days 1 and 15 of Cycle 1 |
| TEmax: Time of Occurrence of Emax | Days 1 and 15 of Cycle 1 |
| Overall Response to Treatment With Ixazomib Citrate Based on Investigator's Evaluation Over Time | Responses were based on International Myeloma Working Group Uniform Criteria. Complete Response (CR)=Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. Partial Response (PR)= reduction in M-Protein ≥50% in serum and ≥90% in 24-hour urine. If M-protein unmeasurable, ≥50% decrease in difference of involved and uninvolved Free Light Chain (FLC). If M-protein and FLC unmeasurable, ≥50% reduction in plasma cells is required, if baseline bone marrow plasma cell ≥30%. And ≥50% reduction in the size of soft tissue plasmacytomas. Minimal Response (MR)= 25-49% reduction in serum paraprotein for 6 weeks. 50-89% reduction in 24 hour urinary light chain excretion for 6 weeks. For Non-secretory myeloma patients, 25-49 % reduction in plasma cells in bone marrow and trephine biopsy for a 6 weeks. 25-49% reduction in the size of soft tissue plasmacytomas. No increase in the size or number of lytic bone lesions. | Up to 354 days |
| West Hollywood |
| California |
| 90069 |
| United States |
| University of Chicago | Chicago | Illinois | 60637 | United States |
| Mayo Clinic | Rochester | Minnesota | 55905 | United States |
| Weill-Cornell Medical College | New York | New York | 10011 | United States |
| Fred Hutchinson Cancer Research Center | Seattle | Washington | 98109 | United States |
| Kumar SK, Bensinger WI, Zimmerman TM, Reeder CB, Berenson JR, Berg D, Hui AM, Gupta N, Di Bacco A, Yu J, Shou Y, Niesvizky R. Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma. Blood. 2014 Aug 14;124(7):1047-55. doi: 10.1182/blood-2014-01-548941. Epub 2014 Jun 5. |
Ixazomib citrate, 0.48 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| FG002 | 0.80 mg/m^2 | Ixazomib citrate, 0.80 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| FG003 | 1.20 mg/m^2 | Ixazomib citrate, 1.20 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| FG004 | 1.68 mg/m^2 | Ixazomib citrate, 1.68 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| FG005 | 2.23 mg/m^2 | Ixazomib citrate, 2.23 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| FG006 | 2.97 mg/m^2 | Ixazomib citrate, 2.97 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| FG007 | 3.95 mg/m^2 | Ixazomib citrate, 3.95 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| FG008 | Relapsed and Refractory (RR) | Ixazomib citrate, 2.97 mg/m^2 established Maximum Tolerated Dose (MTD), capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| FG009 | VELCADE-relapsed (VR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| FG010 | PI naïve | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| FG011 | Carfilzomib | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| COMPLETED |
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| NOT COMPLETED |
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| Expansion Phase |
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Safety Population
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| ID | Title | Description |
|---|---|---|
| BG000 | Overall Study | Safety Population |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Region of Enrollment | Number | participants |
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| Height | Height data was missing for 1 participant. Mean and standard deviation calculation is based on 59 participants. | Mean | Standard Deviation | cm |
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| Weight | Mean | Standard Deviation | kg |
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| Body Surface Area at Baseline | Body Surface Area (BSA) was missing for 1 participant. Mean and standard deviation are based on 59 participants. | Mean | Standard Deviation | m^2 |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Reporting One or More Treatment-Emergent Adverse Events and Serious Adverse Events | An Adverse Event is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A Serious Adverse Event (SAE) was any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. | Safety Population included all randomized participants who received study drug. | Posted | Number | participants | From the first dose through 30 days after last dose of ixazomib citrate or until the start of subsequent antineoplastic therapy (Up to 354 days) |
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| Secondary | Cmax: Maximum Observed Plasma Concentration for MLN2238 | Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). | Participants from the Pharmacokinetic (PK) Analysis Population, all participants who had sufficient dosing data to calculate PK parameters, with data available for calculation of Cmax. | Posted | Mean | Standard Deviation | ng/mL | Days 1 and 15 of Cycle 1 |
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| Secondary | Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for MLN2238 | Tmax: Time to reach the maximum observed plasma concentration (Cmax), equal to time to Cmax. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). | Participants from the PK Analysis Population, all participants who had sufficient dosing data to calculate PK parameters, with data available for analysis of Tmax. | Posted | Median | Full Range | hours | Days 1 and 15 of Cycle 1 |
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| Secondary | AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for MLN2238 | AUC(0-168) is a measure of the area under the plasma concentration-time curve over the dosing interval (tau) (AUC[0-tau]), where tau is the length of the dosing interval - 168 hours in this study). MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). | Participants from the PK Analysis Population, all participants who had sufficient dosing data to calculate PK parameters, with data available for calculation of AUC(0-168). | Posted | Mean | Standard Deviation | hr*ng/mL | Days 1 and 15 of Cycle 1 |
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| Secondary | Accumulation Ratio: Day 15 AUC0-168 / Day 1 AUC0-168 for MLN2238 | MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). | Participants from the PK Analysis Population, all participants who had sufficient dosing data to calculate PK parameters, with data available for calculation of accumulation ratio. | Posted | Mean | Standard Deviation | unitless | Day 15 of Cycle 1 |
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| Secondary | Terminal Elimination Rate Constant (λz) for MLN2238 | Terminal elimination rate constant (λz) is the rate at which drugs are eliminated from the body and the values were used for calculation of T1/2. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). | Participants from the PK Analysis Population, all participants who had sufficient dosing data to calculate PK parameters, with data available for calculation of terminal elimination rate constant. | Posted | Mean | Standard Deviation | 1/hour | Day 15 of Cycle 1 |
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| Secondary | Terminal Phase Elimination Half-life (T1/2) for MLN2238 | Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. MLN2238 is the complete hydrolysis product of the study drug ixazomib citrate (MLN9708). | Participants from the PK Analysis Population, all participants who had sufficient dosing data to calculate PK parameters, with data available for calculation of terminal phase elimination half-life. | Posted | Mean | Standard Deviation | hour | Day 15 of Cycle 1 |
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| Secondary | Emax: Maximum Inhibition | A Whole Blood 20S Proteasome Inhibition Parameter. There were no subjects in the Pharmacodynamic (PD) Analysis Set for the 2.23 mg/m^2 cohort, so PD tables do not include that arm. | PD analysis Population included all participants who had sufficient dosing data to calculate PD parameters | Posted | Mean | Standard Deviation | Percentage of inhibition | Days 1 and 15 of Cycle 1 |
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| Secondary | TEmax: Time of Occurrence of Emax | PD analysis population included all participants who had sufficient dosing data to calculate PD parameters | Posted | Mean | Standard Deviation | Hours | Days 1 and 15 of Cycle 1 |
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| Secondary | Overall Response to Treatment With Ixazomib Citrate Based on Investigator's Evaluation Over Time | Responses were based on International Myeloma Working Group Uniform Criteria. Complete Response (CR)=Negative immunofixation on serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. Partial Response (PR)= reduction in M-Protein ≥50% in serum and ≥90% in 24-hour urine. If M-protein unmeasurable, ≥50% decrease in difference of involved and uninvolved Free Light Chain (FLC). If M-protein and FLC unmeasurable, ≥50% reduction in plasma cells is required, if baseline bone marrow plasma cell ≥30%. And ≥50% reduction in the size of soft tissue plasmacytomas. Minimal Response (MR)= 25-49% reduction in serum paraprotein for 6 weeks. 50-89% reduction in 24 hour urinary light chain excretion for 6 weeks. For Non-secretory myeloma patients, 25-49 % reduction in plasma cells in bone marrow and trephine biopsy for a 6 weeks. 25-49% reduction in the size of soft tissue plasmacytomas. No increase in the size or number of lytic bone lesions. | Response-Evaluable Population included all participants who had measurable disease at Baseline, had received at least 1 dose of study drug, and had at least 1 post-baseline response assessment. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to 354 days |
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| Primary | Neurotoxicity Grading | Neurotoxicity is graded using participant responses to 11 functional questions on a 5-point scale, where 0=Not at all and 4=Very much, using the Functional Assessment of Cancer Therapy/Gynecology Oncology Group - Neurotoxicity Questionnaire, Version 4.0(14). Neurotoxicity subscale is a sum of 11 reversed item scores where each original score is transformed as (4 - score). The highest possible score is 44, and a higher score indicates more neurotoxicity. | Safety Population included all randomized participants who received study drug. | Posted | Mean | Standard Deviation | score on a scale | Cycle 1 Day 1 and End of Study (Up to 354 days) |
|
From the first dose through 30 days after last dose of ixazomib citrate or until the start of subsequent antineoplastic therapy (Up to 354 days)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dose Escalation Cohorts | Ixazomib citrate, 0.24 to 3.95 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Dose Escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. | 7 | 32 | 30 | 32 | ||
| EG001 | Expansion Cohorts | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Expansion Period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. | 15 | 31 | 31 | 31 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Stenosis or Obstruction of Ileus | Gastrointestinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA (15) | Systematic Assessment |
| |
| Hepatitis B | Infections and infestations | MedDRA (15) | Systematic Assessment |
| |
| Abscess Neck | Infections and infestations | MedDRA (15) | Systematic Assessment |
| |
| Parainfluenzae virus infection | Infections and infestations | MedDRA (15) | Systematic Assessment |
| |
| Pneumonia respiratory syncytial viral | Infections and infestations | MedDRA (15) | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA (15) | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA (15) | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA (15) | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA (15) | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA (15) | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA (15) | Systematic Assessment |
| |
| Renal Failure Acute | Renal and urinary disorders | MedDRA (15) | Systematic Assessment |
| |
| Hyperviscosity syndrome | Blood and lymphatic system disorders | MedDRA (15) | Systematic Assessment |
| |
| Cardiac failure congestive | Cardiac disorders | MedDRA (15) | Systematic Assessment |
| |
| Multiple myeloma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA (15) | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA (15) | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Stevens-Johnson syndrome | Skin and subcutaneous tissue disorders | MedDRA (15) | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA (15) | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA (15) | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA (15) | Systematic Assessment |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA (15) | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MedDRA (15) | Systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA (15) | Systematic Assessment |
| |
| Lacrimation increased | Eye disorders | MedDRA (15) | Systematic Assessment |
| |
| Abdominal discomfort | Gastrointestinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Flatulence | Gastrointestinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA (15) | Systematic Assessment |
| |
| Chills | General disorders | MedDRA (15) | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA (15) | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA (15) | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA (15) | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA (15) | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA (15) | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA (15) | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA (15) | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA (15) | Systematic Assessment |
| |
| Blood bicarbonate decreased | Investigations | MedDRA (15) | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA (15) | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA (15) | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA (15) | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA (15) | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA (15) | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA (15) | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA (15) | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA (15) | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA (15) | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA (15) | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (15) | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA (15) | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA (15) | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA (15) | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA (15) | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA (15) | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA (15) | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA (15) | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA (15) | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA (15) | Systematic Assessment |
| |
| Peripheral motor neuropathy | Nervous system disorders | MedDRA (15) | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA (15) | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA (15) | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA (15) | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA (15) | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA (15) | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA (15) | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA (15) | Systematic Assessment |
| |
| Rash papular | Skin and subcutaneous tissue disorders | MedDRA (15) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA (15) | Systematic Assessment |
|
Investigator may publish clinical data after the earlier of publication by Sponsor or 12 months after early termination or database lock. Proposed publication copy should be provided to Sponsor at least 30 days prior to submission/disclosure. If requested, Sponsor's confidential information must be removed and publication delayed if Sponsor intends to file a related patent application.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Takeda | +1-877-825-3327 | trialdisclosures@takeda.com |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| ID | Term |
|---|---|
| D054219 | Neoplasms, Plasma Cell |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C548400 | ixazomib |
Not provided
Not provided
Not provided
| Adverse Event |
|
| Withdrawal by Subject |
|
| Unsatisfactory Therapeutic Response |
|
| Missing |
|
| Other |
|
| OG006 | 2.97 mg/m^2 | Ixazomib citrate, 2.97 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG007 | 3.95 mg/m^2 | Ixazomib citrate, 3.95 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG008 | Relapsed and Refractory (RR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG009 | VELCADE-relapsed (VR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG010 | PI naïve | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG011 | Carfilzomib | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG003 | 1.20 mg/m^2 | Ixazomib citrate, 1.20 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG004 | 1.68 mg/m^2 | Ixazomib citrate, 1.68 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG005 | 2.23 mg/m^2 | Ixazomib citrate, 2.23 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG006 | 2.97 mg/m^2 | Ixazomib citrate, 2.97 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG007 | 3.95 mg/m^2 | Ixazomib citrate, 3.95 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG008 | Relapsed and Refractory (RR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG009 | VELCADE-relapsed (VR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG010 | PI naïve | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG011 | Carfilzomib | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
|
| OG003 | 1.20 mg/m^2 | Ixazomib citrate, 1.20 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG004 | 1.68 mg/m^2 | Ixazomib citrate, 1.68 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG005 | 2.23 mg/m^2 | Ixazomib citrate, 2.23 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG006 | 2.97 mg/m^2 | Ixazomib citrate, 2.97 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG007 | 3.95 mg/m^2 | Ixazomib citrate, 3.95 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG008 | Relapsed and Refractory (RR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG009 | VELCADE-relapsed (VR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG010 | PI naïve | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG011 | Carfilzomib | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
|
Ixazomib citrate, 0.80 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
| OG003 | 1.20 mg/m^2 | Ixazomib citrate, 1.20 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG004 | 1.68 mg/m^2 | Ixazomib citrate, 1.68 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG005 | 2.23 mg/m^2 | Ixazomib citrate, 2.23 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG006 | 2.97 mg/m^2 | Ixazomib citrate, 2.97 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG007 | 3.95 mg/m^2 | Ixazomib citrate, 3.95 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG008 | Relapsed and Refractory (RR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG009 | VELCADE-relapsed (VR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG010 | PI naïve | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG011 | Carfilzomib | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
|
| OG003 | 1.20 mg/m^2 | Ixazomib citrate, 1.20 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG004 | 1.68 mg/m^2 | Ixazomib citrate, 1.68 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG005 | 2.23 mg/m^2 | Ixazomib citrate, 2.23 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG006 | 2.97 mg/m^2 | Ixazomib citrate, 2.97 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG007 | 3.95 mg/m^2 | Ixazomib citrate, 3.95 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG008 | Relapsed and Refractory (RR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG009 | VELCADE-relapsed (VR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG010 | PI naïve | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG011 | Carfilzomib | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
|
| OG003 | 1.20 mg/m^2 | Ixazomib citrate, 1.20 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG004 | 1.68 mg/m^2 | Ixazomib citrate, 1.68 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG005 | 2.23 mg/m^2 | Ixazomib citrate, 2.23 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG006 | 2.97 mg/m^2 | Ixazomib citrate, 2.97 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG007 | 3.95 mg/m^2 | Ixazomib citrate, 3.95 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG008 | Relapsed and Refractory (RR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG009 | VELCADE-relapsed (VR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG010 | PI naïve | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG011 | Carfilzomib | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
|
| OG003 | 1.20 mg/m^2 | Ixazomib citrate, 1.20 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG004 | 1.68 mg/m^2 | Ixazomib citrate, 1.68 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG005 | 2.23 mg/m^2 | Ixazomib citrate, 2.23 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG006 | 2.97 mg/m^2 | Ixazomib citrate, 2.97 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG007 | 3.95 mg/m^2 | Ixazomib citrate, 3.95 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG008 | Relapsed and Refractory (RR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG009 | VELCADE-relapsed (VR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG010 | PI naïve | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG011 | Carfilzomib | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
|
|
| OG003 | 1.20 mg/m^2 | Ixazomib citrate, 1.20 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG004 | 1.68 mg/m^2 | Ixazomib citrate, 1.68 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG005 | 2.23 mg/m^2 | Ixazomib citrate, 2.23 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG006 | 2.97 mg/m^2 | Ixazomib citrate, 2.97 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG007 | 3.95 mg/m^2 | Ixazomib citrate, 3.95 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG008 | Relapsed and Refractory (RR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG009 | VELCADE-relapsed (VR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG010 | PI naïve | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG011 | Carfilzomib | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
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Ixazomib citrate, 1.20 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
| OG004 | 1.68 mg/m^2 | Ixazomib citrate, 1.68 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG005 | 2.23 mg/m^2 | Ixazomib citrate, 2.23 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG006 | 2.97 mg/m^2 | Ixazomib citrate, 2.97 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG007 | 3.95 mg/m^2 | Ixazomib citrate, 3.95 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG008 | Relapsed and Refractory (RR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG009 | VELCADE-relapsed (VR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG010 | PI naïve | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG011 | Carfilzomib | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
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| OG001 |
| 0.48 mg/m^2 |
Ixazomib citrate, 0.48 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG002 | 0.80 mg/m^2 | Ixazomib citrate, 0.80 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG003 | 1.20 mg/m^2 | Ixazomib citrate, 1.20 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG004 | 1.68 mg/m^2 | Ixazomib citrate, 1.68 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG005 | 2.23 mg/m^2 | Ixazomib citrate, 2.23 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG006 | 2.97 mg/m^2 | Ixazomib citrate, 2.97 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG007 | 3.95 mg/m^2 | Ixazomib citrate, 3.95 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG008 | Relapsed and Refractory (RR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG009 | VELCADE-relapsed (VR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG010 | PI naïve | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG011 | Carfilzomib | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
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|
Ixazomib citrate, 0.80 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.
| OG003 | 1.20 mg/m^2 | Ixazomib citrate, 1.20 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG004 | 1.68 mg/m^2 | Ixazomib citrate, 1.68 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG005 | 2.23 mg/m^2 | Ixazomib citrate, 2.23 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG006 | 2.97 mg/m^2 | Ixazomib citrate, 2.97 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG007 | 3.95 mg/m^2 | Ixazomib citrate, 3.95 mg/m^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG008 | Relapsed and Refractory (RR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort that includes 2 participants from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG009 | VELCADE-relapsed (VR) | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort that includes 1 participant from the dose escalation cohort 2.97 mg/m^2. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG010 | PI naïve | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
| OG011 | Carfilzomib | Ixazomib citrate, 2.97 mg/m^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate. |
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