TriangleNCT03275285 · OUTCOME
Progression Free Survival (PFS) As Determined by Independent Response Committee (IRC): Primary Analysis
Results reported by the registry submitting party. Population, time horizon, units and missing values must be read together.
- Measure
- MEDIAN
- Unit
- months
- Interval / dispersion
- 95% Confidence Interval
- Time frame
- From randomization until the primary analysis data cut-off date of 7 Feb 2020 (median duration of follow-up was 20.73 months)
What was measured
Time (in months) from randomization to date of 1st documentation of progressive disease (PD)/date of death from any cause, whichever comes 1st. If PD \& death are not observed before cut-off date/date of initiation of further anti-myeloma treatment, PFS was censored at date of last valid disease assessment not showing PD performed prior to initiation of further anti-myeloma treatment/cut-off date, whichever comes 1st. PD(IMWG criteria):any 1 of following:Increase(inc) of \>=25% in serum M-component from nadir; serum M component inc \>=1 g/dL in 2 consecutive assessment, if starting M component \>=5 g/dL; and/or inc of \>=25% in urine M-component from nadir and/or development of new bone lesion/soft tissue extramedullary disease/inc \>=50% from nadir in sum of perpendicular diameters of existing soft tissue extramedullary disease lesion if \>1 lesion/ \>=50% increase in longest diameter of previous soft tissue extramedullary disease lesion \>1 cm in short axis. Estimated by Kaplan-Meier method.
Analysis population: Analysis was performed on Intent to Treat (ITT) population that included all participants who gave their informed consent and for whom there was a confirmation of successful allocation of a randomization number by the interactive response technology (IRT).
Groups in this outcome
Carfilzomib + Dexamethasone (Kd)
Participants received carfilzomib 20 mg/m\^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m\^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).
Isatuximab + Carfilzomib + Dexamethasone (IKd)
Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m\^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m\^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
| Group | Source count |
|---|---|
| Carfilzomib + Dexamethasone (Kd) | 123 |
| Isatuximab + Carfilzomib + Dexamethasone (IKd) | 179 |
Reported measurements
Source class 1
| Group | Value | Spread | Lower | Upper | Comment |
|---|---|---|---|---|---|
| Carfilzomib + Dexamethasone (Kd) | 19.15 | Not reported | 15.770 | NA | Upper limit of the confidence interval could not be reached due to less number of participants with the events. |
| Isatuximab + Carfilzomib + Dexamethasone (IKd) | NA | Not reported | NA | NA | Median value and the upper and lower limit of the confidence interval could not be calculated because of less than 50% of the participants had PFS events. |
Source statistical analyses
- ci Lower Limit
- 0.318
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 99
- ci Upper Limit
- 0.889
- estimate Comment
- Hazard Ratio was stratified on number of prior lines of therapy (1 vs. \>1) and R-ISS stage (I or II vs. III vs. not classified) according to IRT.
- group Description
- Statistical analysis for comparison of PFS between the Kd and IKd arms based on primary analysis.
- group Ids
- OG000
- OG001
- non Inferiority Comment
- For PFS, the nominal significance levels at primary analysis was determined using alpha-spending function in order to control overall 1-sided type 1 error at 2.5%. The 1-sided nominal significance level to declare overwhelming efficacy at primary analysis (103 PFS events) was 0.005. Because the median PFS was not reached at the primary analysis, it was described at the final analysis.
- non Inferiority Type
- SUPERIORITY
- p Value
- 0.0007
- p Value Comment
- One-sided p-value based on Stratified log-rank test. Threshold for statistical significance at 0.005.
- param Type
- Hazard Ratio (HR)
- param Value
- 0.531
- statistical Comment
- Stratified on number of prior lines of therapy (1 vs \>1) \& revised international staging system stage (I/II vs III vs not classified) as per IRT.
- statistical Method
- Stratified Log-Rank test
Complete source fields
- analyses
- ci Lower Limit
- 0.318
- ci Num Sides
- TWO_SIDED
- ci Pct Value
- 99
- ci Upper Limit
- 0.889
- estimate Comment
- Hazard Ratio was stratified on number of prior lines of therapy (1 vs. \>1) and R-ISS stage (I or II vs. III vs. not classified) according to IRT.
- group Description
- Statistical analysis for comparison of PFS between the Kd and IKd arms based on primary analysis.
- group Ids
- OG000
- OG001
- non Inferiority Comment
- For PFS, the nominal significance levels at primary analysis was determined using alpha-spending function in order to control overall 1-sided type 1 error at 2.5%. The 1-sided nominal significance level to declare overwhelming efficacy at primary analysis (103 PFS events) was 0.005. Because the median PFS was not reached at the primary analysis, it was described at the final analysis.
- non Inferiority Type
- SUPERIORITY
- p Value
- 0.0007
- p Value Comment
- One-sided p-value based on Stratified log-rank test. Threshold for statistical significance at 0.005.
- param Type
- Hazard Ratio (HR)
- param Value
- 0.531
- statistical Comment
- Stratified on number of prior lines of therapy (1 vs \>1) \& revised international staging system stage (I/II vs III vs not classified) as per IRT.
- statistical Method
- Stratified Log-Rank test
- classes
- categories
- measurements
- comment
- Upper limit of the confidence interval could not be reached due to less number of participants with the events.
- group Id
- OG000
- lower Limit
- 15.770
- upper Limit
- NA
- value
- 19.15
- comment
- Median value and the upper and lower limit of the confidence interval could not be calculated because of less than 50% of the participants had PFS events.
- group Id
- OG001
- lower Limit
- NA
- upper Limit
- NA
- value
- NA
- denoms
- counts
- group Id
- OG000
- value
- 123
- group Id
- OG001
- value
- 179
- units
- Participants
- description
- Time (in months) from randomization to date of 1st documentation of progressive disease (PD)/date of death from any cause, whichever comes 1st. If PD \& death are not observed before cut-off date/date of initiation of further anti-myeloma treatment, PFS was censored at date of last valid disease assessment not showing PD performed prior to initiation of further anti-myeloma treatment/cut-off date, whichever comes 1st. PD(IMWG criteria):any 1 of following:Increase(inc) of \>=25% in serum M-component from nadir; serum M component inc \>=1 g/dL in 2 consecutive assessment, if starting M component \>=5 g/dL; and/or inc of \>=25% in urine M-component from nadir and/or development of new bone lesion/soft tissue extramedullary disease/inc \>=50% from nadir in sum of perpendicular diameters of existing soft tissue extramedullary disease lesion if \>1 lesion/ \>=50% increase in longest diameter of previous soft tissue extramedullary disease lesion \>1 cm in short axis. Estimated by Kaplan-Meier method.
- dispersion Type
- 95% Confidence Interval
- groups
- description
- Participants received carfilzomib 20 mg/m\^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m\^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).
- id
- OG000
- title
- Carfilzomib + Dexamethasone (Kd)
- description
- Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m\^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m\^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
- id
- OG001
- title
- Isatuximab + Carfilzomib + Dexamethasone (IKd)
- param Type
- MEDIAN
- population Description
- Analysis was performed on Intent to Treat (ITT) population that included all participants who gave their informed consent and for whom there was a confirmation of successful allocation of a randomization number by the interactive response technology (IRT).
- reporting Status
- POSTED
- time Frame
- From randomization until the primary analysis data cut-off date of 7 Feb 2020 (median duration of follow-up was 20.73 months)
- title
- Progression Free Survival (PFS) As Determined by Independent Response Committee (IRC): Primary Analysis
- type
- PRIMARY
- unit Of Measure
- months
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Preserved source evidence · Not medical advice