NCT01818752 · REGISTRY CONDITION SEARCH

Phase 3 Study of Carfilzomib, Melphalan, Prednisone vs Bortezomib, Melphalan, Prednisone in Newly Diagnosed Multiple Myeloma

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2019-08-26

The primary objective was to compare the progression-free survival of transplant ineligible patients newly diagnosed with multiple myeloma who were treated with carfilzomib, melphalan and prednisone (CMP) or with Velcade® (bortezomib), melphalan and prednisone (VMP).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-Free Survival (PFS)

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Overall Response Rate

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outcome · POSTED

Complete Response Rate

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outcome · POSTED

Percentage of Participants With ≥ Grade 2 Peripheral Neuropathy

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outcome · POSTED

European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores

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outcome · POSTED

Number of Participants With Adverse Events

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: 1. Newly diagnosed symptomatic multiple myeloma (per International Myeloma Working Group \[IMWG\] diagnostic criteria) 2. Transplant ineligibility 3. Measurable disease, as defined by 1 or more of the following (assessed within 21 days prior to randomization): * Serum M-protein ≥ 0.5 g/dL, or * Urine M-protein ≥ 200 mg/24 hours, or * In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) \> 100 mg/L (involved light chain) and an abnormal kappa lambda ratio (SFLC kappa lambda ratio \< 0.26 or \> 1.65) 4. No prior treatment for multiple myeloma 5. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Exclusion Criteria: 1. Multiple myeloma of IgM (immunoglobulin M) subtype 2. Glucocorticoid therapy within 14 days prior to randomization that equals or exceeds a cumulative dose of 160 mg of dexamethasone 3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 4. Plasma cell leukemia (\> 2.0 × 10\^9/L circulating plasma cells by standard differential) 5. Waldenström macroglobulinemia (WM) 6. Known amyloidosis
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants received carfilzomib administered in combination with melphalan and prednisone for nine 42-day cycles. Carfilzomib was administered as an intravenous (IV) infusion on days 1, 2, 8, 9, 22, 23, 29, and 30 of each 42-day cycle. The carfilzomib dose was at 20 mg/m² on cycle 1, days 1 and 2 followed by 36 mg/m² thereafter. On days 1 to 4, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
intervention Names
Drug: Carfilzomib
Drug: Melphalan
Drug: Prednisone
label
Carfilzomib, Melphalan, Prednisone
type
EXPERIMENTAL
description
Participants received bortezomib in combination with melphalan and prednisone for nine 42-day cycles. Bortezomib was administered either IV or subcutaneously at 1.3 mg/m² during cycles 1 to 4 on days 1, 4, 8, 11, 22, 25, 29, and 32 followed by 1.3 mg/m² during cycles 5 to 9 on days 1, 8, 22, and 29. On days 1 to 4 of each cycle, melphalan was administered at 9 mg/m² and prednisone was administered at 60 mg/m².
intervention Names
Drug: Bortezomib
Drug: Melphalan
Drug: Prednisone
label
Bortezomib, Melphalan, Prednisone
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Carfilzomib, Melphalan, Prednisone
description
Carfilzomib was administered over 30 minutes on days 1, 2, 8, 9, 22, 23, 29, and 30 for nine 42-day cycles. Carfilzomib 20 mg/m² IV was administered on days 1 and 2 of cycle 1, followed by escalation to 36 mg/m² IV starting on day 8 of cycle 1.
name
Carfilzomib
other Names
Krypolis®
type
DRUG
arm Group Labels
Bortezomib, Melphalan, Prednisone
description
Bortezomib 1.3 mg/m² was administered as a bolus IV injection or as a subcutaneous injection (per investigator's choice, dose modification, or regulatory approval) on days 1, 4, 8, 11, 22, 25, 29, and 32 of cycles 1 to 4, and on days 1, 8, 22, and 29 of cycles 5 to 9.
name
Bortezomib
other Names
Velcade®
type
DRUG
arm Group Labels
Bortezomib, Melphalan, Prednisone
Carfilzomib, Melphalan, Prednisone
description
Melphalan 9 mg/m² was taken orally on days 1 to 4 of all cycles.
name
Melphalan
type
DRUG
arm Group Labels
Bortezomib, Melphalan, Prednisone
Carfilzomib, Melphalan, Prednisone
description
Prednisone 60 mg/m² was taken orally on days 1 to 4 of all cycles.
name
Prednisone
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 955
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Progression-free survival was defined as the time from randomization to the earlier of documented disease progression or death due to any cause. PFS was analyzed using Kaplan-Meier methods. The duration of PFS was censored for participants with no baseline and/or post-baseline disease assessments, who started a new anti-cancer therapy before documentation of disease progression or death, death or disease progression after missed disease assessment of 100 consecutive days or longer, or who were alive without documentation of disease progression before the data cutoff date, including lost to follow-up prior to disease progression. Participants were evaluated for disease response and progression according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC), determined centrally using a validated computer algorithm in a blinded manner.
measure
Progression-Free Survival (PFS)
time Frame
From randomization until the data cut-off date of 15 July 2016; median follow-up time for PFS was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.

secondary Outcomes

description
Overall survival (OS) was defined as the time from randomization to the date of death (whatever the cause). Participants who were alive or lost to follow-up as of the data analysis cut-off date were censored on the date the patient was last known to be alive. Median overall survival was estimated using the Kaplan-Meier method.
measure
Overall Survival (OS)
time Frame
From randomization until the data cut-off date of 15 July 2016; median follow-up time for OS was 22.2 and 22.5 months in the bortezomib and carfilzomib arms respectively.
description
Disease response was evaluated according to the IMWG-URC using a validated computer algorithm. Overall response was defined as the percentage of participants with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR). sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in BM biopsy; VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein \<100 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline. PR: ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to \< 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.
measure
Overall Response Rate
time Frame
Disease response was assessed every 3 weeks during the first 54 weeks and every 6 weeks thereafter until PD or the data cut-off date of 15 July 2016; median follow-up time was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.
description
Complete response rate was defined as the percentage of participants in each treatment group who achieved a sCR or CR per the IMWG-URC as their best response. sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in BM biopsy.
measure
Complete Response Rate
time Frame
Disease response was assessed every 3 weeks during the first 54 weeks and every 6 weeks thereafter until PD or the data cut-off date of 15 July 2016; median follow-up time was 21.6.and 22.2 months in the bortezomib and carfilzomib arms respectively.
description
Neuropathy events were defined as Grade 2 or higher peripheral neuropathy as specified by peripheral neuropathy Standardised Medical Dictionary for Regulatory Activities (MedDRA) Query, narrow (scope) (SMQN) terms. Peripheral neuropathy was assessed by neurologic exam and graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03: Grade 1: Asymptomatic; Grade 2: Moderate symptoms, limiting instrumental activities of daily living (ADL) Grade 3: Severe symptoms; limiting self-care ADL; Grade 4: Life-threatening consequences, urgent intervention indicated; Grade 5: Death.
measure
Percentage of Participants With ≥ Grade 2 Peripheral Neuropathy
time Frame
From the first dose of any study drug up to 30 days after the last dose of any study drug as of the data cut-off date of 15 July 2016; median duration of treatment was 52 weeks in both treatment groups.
description
The EORTC QLQ-C30 is a validated self-rating questionnaire including 30 items used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, Role, Cognitive, Emotional, Social), and 9 symptom scales/items (Fatigue, Nausea and Vomiting, Pain, Dyspnea, Sleep Disturbance, Appetite Loss, Constipation, Diarrhea, Financial Impact). The EORTC QLQ-C30 Global Health Status/QOL scale was scored between 0 and 100, with higher scores indicating better Global Health Status/QOL.
measure
European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status/Quality of Life (QOL) Scores
time Frame
Baseline, weeks 6, 12, 18, 24, 30, 36, 42 and 48
description
Adverse events (AEs)were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.03, where GRADE 1 = Mild; GRADE 2 = Moderate; GRADE 3 = Severe; GRADE 4 = Life-threatening; GRADE 5 = Fatal. A serious adverse event is an adverse event that met 1 or more of the following criteria: * Death * Life-threatening * Required inpatient hospitalization or prolongation of an existing hospitalization * Resulted in persistent or significant disability/incapacity * Congenital anomaly/birth defect * Important medical event that jeopardized the participant and may have required medical or surgical intervention to prevent 1 of the outcomes listed above. Treatment-related adverse events are adverse events considered related to at least 1 investigational product by the investigator, including those with unknown relationship.
measure
Number of Participants With Adverse Events
time Frame
From the first dose of any study drug up to 30 days after the last dose of any study drug as of the data cut-off date of 15 July 2016; median duration of treatment was 52 weeks in both treatment groups.

Full study description

brief Summary: The primary objective was to compare the progression-free survival of transplant ineligible patients newly diagnosed with multiple myeloma who were treated with carfilzomib, melphalan and prednisone (CMP) or with Velcade® (bortezomib), melphalan and prednisone (VMP).

Source references

references

citation
Chari A, Stewart AK, Russell SD, Moreau P, Herrmann J, Banchs J, Hajek R, Groarke J, Lyon AR, Batty GN, Ro S, Huang M, Iskander KS, Lenihan D. Analysis of carfilzomib cardiovascular safety profile across relapsed and/or refractory multiple myeloma clinical trials. Blood Adv. 2018 Jul 10;2(13):1633-1644. doi: 10.1182/bloodadvances.2017015545.
pmid
29991494
type
BACKGROUND
citation
Facon T, Lee JH, Moreau P, Niesvizky R, Dimopoulos M, Hajek R, Pour L, Jurczyszyn A, Qiu L, Klippel Z, Zahlten-Kumeli A, Osman M, Paiva B, San-Miguel J. Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma. Blood. 2019 May 2;133(18):1953-1963. doi: 10.1182/blood-2018-09-874396. Epub 2019 Feb 28.
pmid
30819926
type
BACKGROUND
citation
Rosenthal A, Luthi J, Belohlavek M, Kortum KM, Mookadam F, Mayo A, Fonseca R, Bergsagel PL, Reeder CB, Mikhael JR, Stewart AK. Carfilzomib and the cardiorenal system in myeloma: an endothelial effect? Blood Cancer J. 2016 Jan 15;6(1):e384. doi: 10.1038/bcj.2015.112.
pmid
26771810
type
DERIVED