Clinical Trial Results:
An Open-label, Phase 2 Study Treating Subjects with First or Second Relapse of Multiple Myeloma with Carfilzomib, Pomalidomide, and Dexamethasone (KPd)
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Summary
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EudraCT number |
2019-001169-34 |
Trial protocol |
DK FR GR ES DE IT |
Global end of trial date |
01 Oct 2024
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Results information
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Results version number |
v1(current) |
This version publication date |
11 Sep 2025
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First version publication date |
11 Sep 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
20180117
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04191616 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Amgen Inc.
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Sponsor organisation address |
One Amgen Center Drive, Thousand Oaks, CA, United States,
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Public contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
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Scientific contact |
IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
01 Oct 2024
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Oct 2024
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the trial was to estimate the overall response rate.
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Protection of trial subjects |
The study protocol and all amendments, the informed consent form, and any accompanying materials provided to the participants were reviewed and approved by an Institutional Review Board (IRB) or Independent Ethics Committee (IEC) at each study center. This study was conducted in accordance with International Council for Harmonisation (ICH) Good Clinical Practice (GCP) regulations/guidelines. The investigator or his/her designee informed the participant of all aspects pertaining to the participant's participation in the study before any screening procedures were performed.
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Background therapy |
Participants may receive intravenous (IV) pre-hydration (normal saline or other appropriate IV fluid) prior to each carfilzomib infusion during cycle 1. Investigators must consider IV pre-hydration in participants at high-risk for tumor lysis or renal toxicity. | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Aug 2020
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Scientific research | ||
Long term follow-up duration |
12 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 4
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Country: Number of subjects enrolled |
France: 5
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Country: Number of subjects enrolled |
Germany: 1
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Country: Number of subjects enrolled |
Greece: 24
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Country: Number of subjects enrolled |
Italy: 7
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Country: Number of subjects enrolled |
Spain: 7
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Country: Number of subjects enrolled |
United States: 6
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Worldwide total number of subjects |
54
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EEA total number of subjects |
48
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
23
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From 65 to 84 years |
30
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85 years and over |
1
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Recruitment
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Recruitment details |
Participants were enrolled at 25 study centers in Denmark, France, Germany, Greece, Italy, Spain, and the United States from 06 August 2020 to 01 October 2024. | ||||||||||||||
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Pre-assignment
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Screening details |
Participants with relapsed multiple myeloma whose disease was refractory to lenalidomide were enrolled. | ||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
54 | ||||||||||||||
Number of subjects completed |
52 | ||||||||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
Did not receive study treatment: 2 | ||||||||||||||
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Period 1
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Period 1 title |
Treatment period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||
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Arms
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Arm title
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Carfilzomib with Pomalidomide and Dexamethasone (KPd) | ||||||||||||||
Arm description |
Carfilzomib was administered intravenously on days 1, 8, and 15 (± 2 days) of each 28-day cycle for up to 12 cycles or progression or end of study. A dose of 20 mg/m^2 was administered on day 1 of cycle 1; all subsequent doses were 56 mg/m^2. From cycle 13, the frequency of carfilzomib administration was reduced to days 1 and 15 (± 2 days) per cycle until progression or end of study. Dexamethasone was administered orally or intravenously at a dose of 40 mg on days 1, 8, 15, and 22 of each cycle during cycles 1 to 12, and at a dose of 20 mg on days 1 and 15 from cycle 13 until progression or end of study. Pomalidomide 4 mg was administered orally on days 1 to 21 of each cycle until progression or end of study. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Carfilzomib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Carfilzomib was administered intravenously on days 1, 8, and 15 (± 2 days) of each 28-day cycle for up to 12 cycles or progression or end of study. A dose of 20 mg/m^2 was administered on day 1 of cycle 1; all subsequent doses were 56 mg/m^2. From cycle 13, the frequency of carfilzomib administration was reduced to days 1 and 15 (± 2 days) per cycle until progression or end of study.
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Investigational medicinal product name |
Dexamethasone
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet, Solution for infusion, Solution for injection
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Routes of administration |
Oral use, Intramuscular and intravenous use
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Dosage and administration details |
Dexamethasone was administered orally or intravenously at a dose of 40 mg on days 1, 8, 15, and 22 of each cycle during cycles 1 to 12, and at a dose of 20 mg on days 1 and 15 from cycle 13 until progression or end of study.
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Investigational medicinal product name |
Pomalidomide
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Pomalidomide 4 mg was administered orally on days 1 to 21 of each cycle until progression or end of study.
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: The number of participants in the baseline period is equal to the number of participants who received study treatment. |
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Baseline characteristics reporting groups
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Reporting group title |
Carfilzomib with Pomalidomide and Dexamethasone (KPd)
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Reporting group description |
Carfilzomib was administered intravenously on days 1, 8, and 15 (± 2 days) of each 28-day cycle for up to 12 cycles or progression or end of study. A dose of 20 mg/m^2 was administered on day 1 of cycle 1; all subsequent doses were 56 mg/m^2. From cycle 13, the frequency of carfilzomib administration was reduced to days 1 and 15 (± 2 days) per cycle until progression or end of study. Dexamethasone was administered orally or intravenously at a dose of 40 mg on days 1, 8, 15, and 22 of each cycle during cycles 1 to 12, and at a dose of 20 mg on days 1 and 15 from cycle 13 until progression or end of study. Pomalidomide 4 mg was administered orally on days 1 to 21 of each cycle until progression or end of study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Carfilzomib with Pomalidomide and Dexamethasone (KPd)
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Reporting group description |
Carfilzomib was administered intravenously on days 1, 8, and 15 (± 2 days) of each 28-day cycle for up to 12 cycles or progression or end of study. A dose of 20 mg/m^2 was administered on day 1 of cycle 1; all subsequent doses were 56 mg/m^2. From cycle 13, the frequency of carfilzomib administration was reduced to days 1 and 15 (± 2 days) per cycle until progression or end of study. Dexamethasone was administered orally or intravenously at a dose of 40 mg on days 1, 8, 15, and 22 of each cycle during cycles 1 to 12, and at a dose of 20 mg on days 1 and 15 from cycle 13 until progression or end of study. Pomalidomide 4 mg was administered orally on days 1 to 21 of each cycle until progression or end of study. | ||
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End point title |
Overall Response Rate (ORR) as Assessed by the Independent Review Committee (IRC) [1] | ||||||||
End point description |
Overall response was defined as the best overall confirmed response of: Complete response (CR): Negative immunofixation on serum and urine, soft tissue plasmacytomas disappearance, < 5% plasma cells in bone marrow (BM). Stringent CR (sCR): CR and normal serum free light chain ratio and no clonal cells in BM. Very Good Partial Response (VGPR): Serum and urine M-protein detectable by immunofixation or ≥ 90% reduction in serum M-protein (urine M-protein level < 100 mg/24-h). PR: ≥ 50% reduction of serum M-protein and 24-h urinary M-protein by ≥ 90% or to < 200 mg/24-h. Assessment was by IRC per International Myeloma Working Group Uniform Response Criteria (IMWG-URC). The 90% confidence intervals were estimated using the Clopper-Pearson method (1994).
The safety analysis set included all participants who received at least 1 dose of carfilzomib.
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End point type |
Primary
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End point timeframe |
From day 1 cycle 1 until the primary analysis (PA) data cutoff (DCO); the mean duration of KPd treatment as of the DCO was 42.0 weeks
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Formal comparative statistical analysis was not pre-specified for this outcome measure. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants with Treatment-emergent Adverse Events (TEAEs) | ||||||
End point description |
TEAEs were defined as events with onset on or after the administration of the first dose of any study treatment and within the end of study, or 30 days after the last dose of any study treatment, whichever one was earlier, excluding events reported after end of study date.
The safety analysis set included all participants who received at least 1 dose of carfilzomib.
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End point type |
Secondary
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End point timeframe |
From the first dose of any study treatment until the end of study or 30 days after the last dose of any study treatment, whichever occured earlier; Median (min, max) was 8.5 (1.0, 46.6) months
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| No statistical analyses for this end point | |||||||
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End point title |
Percentage of Participants with a Minimal Residual Disease Negative Complete Response (MRD[-]CR) as Assessed by the IRC | ||||||||
End point description |
The MRD[-]CR rate was defined as the percentage of participants who reached MRD[-]CR at the 12 month landmark (8- to 13-month window). MRD[-]CR was defined as the achievement of CR (including sCR or better) per IMWG-URC by IRC assessment and MRD[-] status at a sensitivity of 10^-5 using next-generation sequencing based method in the bone marrow. The 90% CIs were estimated using the Clopper-Pearson method (1994).
The safety analysis set included all participants who received at least 1 dose of carfilzomib. The analysis was pre-specified until PA DCO only.
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End point type |
Secondary
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End point timeframe |
Day 1 cycle 1 to month 12 (8 to 13 month window)
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| No statistical analyses for this end point | |||||||||
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End point title |
Kaplan-Meier Estimate of Progression Free Survival (PFS) as Assessed by the IRC | ||||||||
End point description |
PFS was defined as time from start of treatment until progression or death from any cause. Medians and percentiles were estimated using the Kaplan-Meier method by Klein and Moeschberger (1997). 90% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.
9999 = Result was not estimable.
The safety analysis set included all participants who received at least 1 dose of carfilzomib.
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End point type |
Secondary
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End point timeframe |
From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Kaplan-Meier Estimate of Duration of Response as Assessed by the IRC | ||||||||
End point description |
Disease response and progression were determined using IMWG-URC. Durations were calculated for responders. Medians and percentiles were estimated using the Kaplan-Meier method. 90% CIs for medians and percentiles were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.
9999 = Result was not estimable.
The safety analysis set included all participants who received at least 1 dose of carfilzomib. Only participants who achieved a partial response or better were included in the analysis.
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End point type |
Secondary
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End point timeframe |
From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Response as Assessed by the IRC | ||||||||
End point description |
Durations were calculated for responders. Time to response was defined as the time from start of any study treatment date to the earliest date when confirmed sCR, CR, VGPR, or partial response (PR) was first achieved.
The safety analysis set included all participants who received at least 1 dose of carfilzomib. Only participants who achieved a partial response or better were included in the analysis.
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End point type |
Secondary
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End point timeframe |
From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks
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| No statistical analyses for this end point | |||||||||
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End point title |
Kaplan-Meier Estimate of Overall Survival (OS) | ||||||||
End point description |
OS was defined as the time from the start of treatment until death from any cause. Medians and percentiles were estimated using the Kaplan-Meier method. 90% CIs for medians were estimated using the method by Klein and Moeschberger (1997) with log-log transformation.
The safety analysis set included all participants who received at least 1 dose of carfilzomib.
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End point type |
Secondary
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End point timeframe |
From day 1 cycle 1 until the EOS; the mean duration of KPd treatment was 55.3 weeks.
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants Achieving MRD[-] Response | ||||||
End point description |
MRD[-] response was defined as achievement of MRD[-] status using next generation sequencing (NGS) based method in the bone marrow at any time.
The safety analysis set included all participants who received at least 1 dose of carfilzomib.
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End point type |
Secondary
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End point timeframe |
From day 1 cycle 1 until the end of study (EOS); the mean duration of KPd treatment as of the EOS was 55.3 weeks
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants with Sustained MRD[-]CR for at Least 12 Months as Assessed by the IRC | ||||||
End point description |
MRD[-]CR at the 12 months landmark was defined as achievement of CR (including sCR or better) per IMWG-URC by IRC and MRD[-] status at a sensitivity of 10^-5 using NGS based method in the bone marrow at the 12 months landmark (from 8 months to 13 months window). Maintaining MRD[-]CR for at least 12 months (- 4 weeks) was considered as sustained.
The safety analysis set included all participants who received at least 1 dose of carfilzomib.
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End point type |
Secondary
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End point timeframe |
Day 1 cycle 1 to month 12 (8 to 13 month window)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants with Sustained MRD[-]CR at Month 24 as Assessed by the IRC | ||||||
End point description |
Sustained MRD[-]CR at 24 months included participants that maintained MRD[-]CR for 12 months or more after achieving MRD[-]CR status at 12 months.
The safety analysis set included all participants who received at least 1 dose of carfilzomib.
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End point type |
Secondary
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End point timeframe |
Day 1 cycle 1 to month 26 (19 to 26 month window)
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| No statistical analyses for this end point | |||||||
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End point title |
Number of Participants with Best Overall Confirmed Response of CR or Better as Assessed by the IRC | ||||||
End point description |
The number of safety analysis set participants whose best overall response was sCR or CR per IMWG-URC over the duration of the study.
The safety analysis set included all participants who received at least 1 dose of carfilzomib.
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End point type |
Secondary
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End point timeframe |
From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks
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| No statistical analyses for this end point | |||||||
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Adverse events information
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Timeframe for reporting adverse events |
Death: 1st study drug to EOS, also after EOS; Median (min, max) was 16.5 (1.0, 47.0) months. Adverse events: 1st dose of any study treatment to earliest of EOS or 30 days after last dose of any study treatment; Median (min, max) was 8.5 (1.0, 46.6) months
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Adverse event reporting additional description |
All-cause mortality is reported for all participants enrolled in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
27.0
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Reporting groups
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Reporting group title |
Carfilzomib with Pomalidomide and Dexamethasone (KPd)
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Reporting group description |
Carfilzomib was administered intravenously on days 1, 8, and 15 (± 2 days) of each 28-day cycle for up to 12 cycles or progression or end of study. A dose of 20 mg/m^2 was administered on day 1 of cycle 1; all subsequent doses were 56 mg/m^2. From cycle 13, the frequency of carfilzomib administration was reduced to days 1 and 15 (± 2 days) per cycle until progression or end of study. Dexamethasone was administered orally or intravenously at a dose of 40 mg on days 1, 8, 15, and 22 of each cycle during cycles 1 to 12, and at a dose of 20 mg on days 1 and 15 from cycle 13 until progression or end of study. Pomalidomide 4 mg was administered orally on days 1 to 21 of each cycle until progression or end of study. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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17 Sep 2019 |
• Cohort 1: Carfilzomib, Daratumumab, and Dexamethasone was removed.
• Hepatic Insufficiency for pomalidomide was added.
• Secondary endpoint of frequency of sustained MRD response was added.
• Statistical analysis section was updated to include 12 month landmark.
• Objectives and endpoints were clarified.
• NGS-based method for evaluating MRD was added.
• Title of protocol was updated to include second relapse.
• IRC was added.
• Number of subjects and number of sites were updated.
• Study rationale and benefit/risk sections were updated with updated data.
• Bone targeting agents were added to recommended therapies. |
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13 May 2020 |
• Prophylaxis for Hepatitis B virus reactivation to other protocol-required therapies was added.
• Hepatitis B dose modification was added.
• MRD assessments were changed from a ± 2-week window, to a ± 4-week window.
• The primary objective was updated from estimating the efficacy by rate of MRD[-] response of KPd to estimating the rate of MRD[-]CR.
• Screening was updated regarding fetal toxicity, beginning 4 weeks prior to initiating treatment with pomalidomide.
• Clarifications were made to PFS, OS, and CR in efficacy analyses.
• Dose modification in abnormalities from tumor lysis syndrome were added.
• Windows for radiological plasmacytoma assessments were extended from every 12 weeks to every 12 weeks ± 2 weeks.
• Screening evaluations for disease specific assessments, measurable disease, rescreening, echocardiograms, pulmonary function tests, bone lesions, and plasmacytomas were changed from 30 to 28 days.
• 2 contraceptive methods were removed to align with the Summary of Product Characteristics for pomalidomide: (1) intrauterine devices and (2) combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation.
• Reporting requirement for start and stop time of Pomalidomide administration was removed. |
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26 Mar 2021 |
• The requirement of daratumumab exposure was removed.
• The ORR was updated as a key secondary endpoint to further designate this endpoint as clinically important and pre-specify the order for analysis.
• The number of sites were updated from 35 to 45.
• The carfilzomib dose modification guidelines for nonhematologic toxicities were updated.
• The statistical considerations were updated, given newly available data that includes outcomes of subjects who are refractory to lenalidomide.
• The safety reporting and birth control requirements were updated per the current protocol template. |
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16 May 2022 |
• Primary endpoint was changed to ORR, and MRD[-] CR rate was moved to secondary endpoint.
• The hypothesis and statistical consideration sections were updated to align with updated endpoints.
• Pomalidomide modification guidelines were updated for nonhematologic toxicities.
• Statements on discontinuation of recruitment after 54 subjects enrolled were added; decision was made because of challenges to enrollment in part due to evolving changes in multiple myeloma treatment landscape. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
