Study of Early Relapsed, Lenalidomide-refractory Subjects Eligible for Carfilzomib Triplet (SELECT)
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| ClinicalTrials.gov Identifier: NCT04191616 |
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Recruitment Status :
Active, not recruiting
First Posted : December 10, 2019
Results First Posted : November 8, 2023
Last Update Posted : February 8, 2024
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Relapsed or Refractory Multiple Myeloma | Drug: Carfilzomib Drug: Dexamethasone Drug: Pomalidomide | Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 54 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | An Open-label, Phase 2 Study Treating Subjects With First or Second Relapse of Multiple Myeloma With Carfilzomib, Pomalidomide, and Dexamethasone (KPd) |
| Actual Study Start Date : | August 6, 2020 |
| Actual Primary Completion Date : | November 30, 2022 |
| Estimated Study Completion Date : | October 1, 2024 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Carfilzomib combined with pomalidomide and dexamethasone
Carfilzomib, pomalidomide, and dexamethasone (KPd)
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Drug: Carfilzomib
Carfilzomib will be administered intravenously over 30 ± 5 minutes, on days 1, 8, and 15 (± 2 days) of each 28-day cycle for up to 12 cycles or progression. A dose of 20 mg/m^2 will be administered on day 1 of cycle 1. All subsequent doses will be 56 mg/m^2. The frequency of carfilzomib administration will be reduced to day 1 and 15 per cycle starting with cycle 13 and continued until progression or end of study.
Other Name: Kyprolis Drug: Dexamethasone Dexamethasone will be administered at least 30 minutes, but no more than 4 hours prior to carfilzomib on days of carfilzomib administration. Dexamethasone will be administered at a dose of 40 mg on days 1, 8, 15, and 22 of each 28-day cycle up to progression during cycles 1 to 12. Dexamethasone will be administered at a dose of 20 mg on days 1 and 15 of each 28-day cycle up to progression during cycles 13 onward. For subjects more than or equal to 75 years of age, the dose will be 20 mg during cycles 1 through 12 and 10 mg from cycles 13 onward.
Other Name: Decadron, Ozurdex, DexPak 6, 10, 13 Day, ReadySHarp, LoCort, Maxidex Drug: Pomalidomide Pomalidomide dose will be 4 mg per day orally on days 1 to 21 of each cycle until progression.
Other Name: Pomalyst |
- Overall Response Rate (ORR) As Assessed by the Independent Review Committee (IRC) (PA DCO Only) [ Time Frame: From day 1 cycle 1 until the PA DCO date of 30 November 2022; the median duration of KPd treatment as of the DCO was 32.8 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).
- Percentage of Participants With a Minimal Residual Disease Negative Complete Response (MRD[-]CR) as Assessed by the IRC (PA DCO Only) [ Time Frame: Day 1 cycle 1 to month 12 (8 to 13 month window). PA DCO date of 30 November 2022; the median duration of KPd treatment as of the DCO was 32.8 weeks. ]The MRD[-]CR rate was defined as the number 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 [ Time Frame: Day 1 cycle 1 up to approximately 60 months ]
- Number of Participants Achieving Minimal Residual Disease Negative MRD[-] Response [ Time Frame: Day 1 cycle 1 to month 60 ]
- Number of Participants With Sustained MRD[-]CR for at Least 12 Months as Assessed by the IRC [ Time Frame: Day 1 cycle 1 to month 60 ]
- Number of Participants With Sustained MRD[-]CR at Month 24 as Assessed by the IRC [ Time Frame: Day 1 cycle 1 to month 26 (19 to 26 month window) ]
- Kaplan-Meier Estimate of Duration of Response as Assessed by the IRC [ Time Frame: Day 1 cycle 1 to month 60 ]
- Time to Response as Assessed by the IRC [ Time Frame: Day 1 cycle 1 to month 60 ]
- Kaplan-Meier Estimate of Progression Free Survival as Assessed by the IRC [ Time Frame: Day 1 cycle 1 to month 60 ]
- Kaplan-Meier Estimate of Overall Survival [ Time Frame: Day 1 cycle 1 to month 60 ]
- Number of Participants With Best Overall Confirmed Response of CR or Better as Assessed by the IRC [ Time Frame: Day 1 cycle 1 to month 60 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 99 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria
- Subject has provided informed consent prior to initiation of any study specific activities or procedures.
- Male or female subjects age ≥ 18 years
- First or second relapse of multiple myeloma by IMWG criteria (subjects refractory to the most recent line of therapy, excluding carfilzomib, are eligible)
- Refractory to lenalidamide
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Measurable disease with at least 1 of the following assessed within 28 days prior to enrollment:
- IgG multiple myeloma: serum monoclonal protein (M-protein) level ≥ 1.0 g/dL
- IgA, IgD, IgE multiple myeloma: serum M-protein level ≥ 0.5 g/dL
- urine M-protein ≥ 200 mg per 24 hours
- in subjects without measurable serum or urine M-protein, serum-free light chain (SFLC) ≥ 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio
- Must have at least a PR to at least 1 line of prior therapy
- Prior therapy with proteasome inhibitors is allowed. Subjects receiving prior carfilzomib therapy must have achieved at least a PR, was not removed due to toxicity, did not relapse within 60 days from discontinuation of carfilzomib, and must have at least a 6 month carfilzomib treatment-free interval from their last dose of carfilzomib
- ECOG PS of 0 to 2
Exclusion Criteria
- Primary refractory multiple myeloma
- Waldenström macroglobulinemia
- Multiple myeloma of IgM subtype
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Plasma cell leukemia ( greater than 2.0 × 109/L circulating plasma cells by differential). If automated differential shows ≥ 20% of other cells, obtain manual differential to identify other cells.
- Primary amyloidosis (patients with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all other criteria are met)
- Previous diagnosis of amyloidosis associated with myeloma
- Myelodysplastic syndrome
- Toxicity requiring discontinuation of lenalidomide therapy
- Prior treatment with pomalidomide
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04191616
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| Study Director: | MD | Amgen |
Documents provided by Amgen:
| Responsible Party: | Amgen |
| ClinicalTrials.gov Identifier: | NCT04191616 |
| Other Study ID Numbers: |
20180117 2019-001169-34 ( EudraCT Number ) |
| First Posted: | December 10, 2019 Key Record Dates |
| Results First Posted: | November 8, 2023 |
| Last Update Posted: | February 8, 2024 |
| Last Verified: | February 2024 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) |
| Time Frame: | Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study. |
| Access Criteria: | Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below. |
| URL: | http://www.amgen.com/datasharing |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Multiple Myeloma RRMM Open-label First Relapse Multiple Myeloma Second Relapse Multiple Myeloma |
Refractory to Lenalidomide Triplicate Treatment Regimen Dexamethasone Carfilzomib Pomalidomide |
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Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Dexamethasone |
Pomalidomide Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Immunologic Factors Angiogenesis Inhibitors Angiogenesis Modulating Agents |