Study of Early Relapsed, Lenalidomide-refractory Subjects Eligible for Carfilzomib Triplet

Phase 2

Completed

Conditions: Relapsed or Refractory Multiple Myeloma

Interventions: Drug: Carfilzomib
Drug: Dexamethasone
Drug: Pomalidomide

Registration Number: NCT04191616

Lead Sponsor: Amgen

Brief Summary: A Study Evaluating Treatment of Multiple Myeloma with Carfilzomib in Combination with Pomalidomide and Dexamethasone

Detailed Description: An Open-label, Phase 2 Study Treating Subjects with First or Second Relapse of Multiple Myeloma with Carfilzomib, Pomalidomide, and Dexamethasone (KPd)

This trial is designed to estimate the efficacy of a carfilzomib-based triplet in first or second relapse of multiple myeloma for subjects refractory to lenalidomide. The study is an open-label, phase 2 trial. Subjects may receive treatment until progression.

Myeloma disease status will be monitored locally for response and progression per International Myeloma Working Group (IMWG) criteria (Kumar et al, 2016) every 28 ± 7 days from cycle 1 day 1 until confirmed progressive disease (PD), death, lost to follow-up, or withdrawal of full consent (whichever occurs first), regardless of cycle duration, dose delays or treatment discontinuation. Subjects with a suspected complete response (CR) or better will have a bone marrow for minimal residual disease (MRD) assessment at 12 and 24 months (± 4 weeks) from start of treatment (unless a MRD assessment was performed within 4 months before planned assessment).

Subjects who end study drug(s) without confirmed PD are required to complete disease response assessments and report new anti-myeloma treatment every 28 ± 7 days until first subsequent anti-myeloma treatment, death, lost to follow-up, withdrawal of full consent, confirmed PD, or end of study, whichever occurs first. Subjects who discontinue treatment and either start new anti-myeloma treatment or have PD will enter long-term follow-up every 12 weeks until death or end of study.

Approximately one-third of subjects enrolled in the study will be in first relapse and two-thirds in second relapse.

This study will enroll adults ≥ 18 years of age with first or second relapse multiple myeloma.

Eligible subjects will have relapsed multiple myeloma after receiving 1 or 2 prior lines of therapy.

Subjects must be refractory to lenalidomide. Subjects may not have received prior pomalidomide. Prior exposure to a proteasome inhibitor is allowed. Subjects previously exposed to carfilzomib must have responded with at least a partial response to carfilzomib, must not have discontinued carfilzomib due to toxicity, may not have relapsed while receiving or within 60 days of the last dose of carfilzomib, and must have at least a 6 month carfilzomib treatment-free interval since their last dose of carfilzomib.

Subjects must have measurable disease per IMWG consensus criteria, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 2, and at least partial response to 1 line of therapy.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 54

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Carfilzomib combined with pomalidomide and dexamethasone	Pomalidomide	Carfilzomib, pomalidomide, and dexamethasone (KPd)
Carfilzomib combined with pomalidomide and dexamethasone	Carfilzomib	Carfilzomib, pomalidomide, and dexamethasone (KPd)
Carfilzomib combined with pomalidomide and dexamethasone	Dexamethasone	Carfilzomib, pomalidomide, and dexamethasone (KPd)

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR) As Assessed by the Independent Review Committee (IRC)	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	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).

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With a Minimal Residual Disease Negative Complete Response (MRD[-]CR) as Assessed by the IRC	Day 1 cycle 1 to month 12 (8 to 13 month window)	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).
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	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	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.
Number of Participants Achieving MRD[-] Response	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	MRD\[-\] response was defined as achievement of MRD\[-\] status using next generation sequencing (NGS) based method in the bone marrow at any time.
Number of Participants With Sustained MRD[-]CR for at Least 12 Months as Assessed by the IRC	Day 1 cycle 1 to month 12 (8 to 13 month window)	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.
Number of Participants With Sustained MRD[-]CR at Month 24 as Assessed by the IRC	Day 1 cycle 1 to month 26 (19 to 26 month window)	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.
Kaplan-Meier Estimate of Duration of Response as Assessed by the IRC	From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks	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.
Time to Response as Assessed by the IRC	From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks	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, very good partial response (VGPR), or partial response (PR) was first achieved.
Kaplan-Meier Estimate of Progression Free Survival (PFS) as Assessed by the IRC	From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks	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.
Kaplan-Meier Estimate of Overall Survival (OS)	From day 1 cycle 1 until the EOS; the mean duration of KPd treatment was 55.3 weeks.	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.
Number of Participants With Best Overall Confirmed Response of CR or Better as Assessed by the IRC	From day 1 cycle 1 until the PA DCO; the mean duration of KPd treatment as of the DCO was 42.0 weeks	The number of safety analysis set participants whose best overall response was sCR or CR per IMWG-URC over the duration of the study.

Trial Locations

Locations (46): University of Alabama at Birmingham
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Birmingham, Alabama, United States
Rocky Mountain Cancer Centers Denver Midtown
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Denver, Colorado, United States
Yale Cancer Center
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New Haven, Connecticut, United States
Affiliated Oncologists, LLC
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Chicago Ridge, Illinois, United States
Minnesota Oncology Hematology PA
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Saint Paul, Minnesota, United States
Oncology Hematology Care Incorporated
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Cincinnati, Ohio, United States
Texas Oncology - Austin Midtown
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Austin, Texas, United States
United States Oncology Regulatory Affairs Corporate Office
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Austin, Texas, United States
US Oncology Research Investigational Products Center
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Austin, Texas, United States
Baylor Charles A Sammons Cancer Center at Dallas
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Dallas, Texas, United States
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University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States