Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Dexamethasone acetate

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Participants will receive carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter).

Participants will also receive 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23 of each cycle.

Participants will receive treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, non-compliance, or intercurrent illness or worsening of a chronic condition, whichever occurs first.

20 mg intravenous (IV) or oral dexamethasone on days 1, 2, 8, 9, 15, 16, 22, and 23 in 28-day cycles.

Infusion of IV carfilzomib on days 1, 2, 8, 9, 15 and 16 in each 28-day cycle.

Carfilzomib

The purpose of this study is to evaluate the safety, tolerability and overall response rate of carfilzomib in combination with dexamethasone for the treatment of multiple myeloma in China.

Carfilzomib in Combination With Dexamethasone (Kd) in Chinese Patients With Relapsed & Refractory Multiple Myeloma

An Open-label, Single-arm, Phase 3 Study of Carfilzomib in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma in China

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria.

sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and \< 5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC.

VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein \<100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC).

PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to \< 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline.

Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to International Myeloma Working Group Uniform Response Criteria (IMWG-URC) (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).

MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a \>50% reduction in the size of soft tissue plasmacytomas is also required

Clinical benefit rate (CBR) is defined as the percentage of participants with the best overall response of minimal response (MR) or better according to IMWG-URC criteria (i.e., a minimal response, partial response, very good partial response, complete response, or stringent complete response).

MR: 25% to 49% reduction in the level of serum M-protein and a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour; If present at baseline, a \>50% reduction in the size of soft tissue plasmacytomas was also required.

Duration of response (DOR) is defined as the time from first evidence of PR or better to disease progression (PD) or death due to any cause per the IMWG-URC criteria.

PD:

* Increase of 25% from lowest response value in any of the following:

  * Serum M-component (absolute increase ≥ 0.5 g/dL) and/or
  * Urine M-component (absolute increase ≥ 200 mg/24 hours)
  * In patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved FLC levels (absolute increase \>10 mg/dL)
* Definite development of new or increase in size of existing bone lesions or soft tissue plasmacytomas
* Development of hypercalcemia attributed solely to the plasma cell proliferative disorder.

DOR was analyzed using the Kaplan-Meier method; Participants with no documented progression or death were censored at the date of their last disease assessment.

DOR was determined based on both investigator and independent review committee response assessments.

Duration of clinical benefit (DCB) is defined as the time from first evidence of MR or better to disease progression or death due to any cause based on the (IMWG-URC criteria. DCB was estimated using the Kaplan-Meier method; participants with no disease progression or death at the analysis cut-off date were censored at their last disease assessment date.

Duration of clinical benefit was determined based on both investigator and independent review committee response assessments.

Progression-free survival (PFS) is defined as the time from first dose of any study treatment to the earlier of disease progression or death due to any cause according to the IMWG-URC criteria. PFS was analyzed using the Kaplan-Meier method; participants with no disease progression or death at the time of the data cut-off date were censored at the date of their last disease assessment; participants who started new anti-cancer therapy before disease progression or death were censored at their last disease assessment prior to starting new anti-cancer therapy.

Progression-free survival was determined based on both investigator and independent review committee response assessments.

Overall survival (OS) is defined as the time from the first dose of any study treatment to the date of death due to any cause. Overall survival was analyzed using the Kaplan-Meier method; participants who were alive or lost to follow-up as of the data analysis cut-off date were censored at their date of last contact (last known to be alive).

Time to response (TTR) is the time from the first dose of any study treatment to the first confirmed response (PR or better) based on both investigator and independent review committee response assessments.

Cmax is the maximum observed plasma concentration over the concentration-time profile of carfilzomib.

Tmax of carfilzomib is the time at which maximum observed plasma concentrations of carfilzomib were observed.

AUClast of carfilzomib is the total area under the concentration-time curve beginning from time 0 to the time of the last measurable concentration of carfilzomib.

AUC0-inf of carfilzomib is the total area under the concentration-time curve beginning from time 0 extrapolated to infinity following carfilzomib dosing.

The terminal elimination half-life is the time required for plasma concentrations to fall by 50% in the terminal phase of the concentration-time profile.

Systemic clearance is a measure of the ability of the body to eliminate drug, expressed in units of volume per time.

Volume of distribution is a pharmacokinetic parameter relating the amount of drug in the body to the concentration of drug in plasma.

Volume of distribution at steady-state is a pharmacokinetic parameter that relates the amount of drug in the body at steady-state to the concentration of drug in the plasma.

MRTlast is the mean residence time observed from time 0 until the time of the last quantifiable concentration.

Onyx Therapeutics, Inc.

Amgen

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.

Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 20 mg dexamethasone IV or orally on days 1, 2, 8, 9, 15, 16, 22, and 23.

Participants received treatment until disease progression, unacceptable toxicity, initiation of new antimyeloma therapy, withdrawal of consent, subject noncompliance, or intercurrent illness or worsening of a chronic condition, whichever occurred first.

Carfilzomib With Dexamethasone

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

A scale to assess a patient's disease status. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care, unable to carry out any work activities. Up and about \> 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair \> 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead.

Eastern Cooperative Oncology Group (ECOG) Performance Status

One participant had a data entry error with year of diagnosis entered as 2017 instead of 2014, leading to an erroneous minimum time since diagnosis reported.

Time From Initial Diagnosis to First Dose

Total Number of Prior Regimens

The safety population consisted of all enrolled participants who received at least 1 dose of carfilzomib.

Study Director

Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee

Overall Response Rate (ORR) After at Least 6 Cycles of Treatment Assessed by the Investigator

Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee

Overall Response Rate After at Least 12 Cycles of Treatment Assessed by the Investigator

Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Independent Review Committee

Clinical Benefit Rate After at Least 6 Cycles of Treatment Assessed by the Investigator

Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Independent Review Committee

Clinical Benefit Rate After at Least 12 Cycles of Treatment Assessed by the Investigator

Independent Review Committee Assessment

Investigator Assessment

Safety population participants who achieved an overall response (best response of PR or better)

Duration of Overall Response (DOR)

Safety population participants who achieved a best overall response of minimal response or better.

Duration of Clinical Benefit (DCB)

Progression-free Survival (PFS)

Overall Survival (OS)

Time to Response (TTR)

Cycle 1 Day 1 (20 mg/m²)

Cycle 2 Day 1 (27 mg/m²)

Pharmacokinetic (PK) analyses were conducted on a subset of participants at selected sites. The PK analysis population included participants who received at least 1 dose of carfilzomib and had adequate data for the noncompartmental estimation of PK parameters. Results are reported for participants with available data at each time point.

Maximum Observed Plasma Concentration (Cmax) of Carfilzomib

Time to Maximum Plasma Concentration (Tmax) of Carfilzomib

Area Under the Plasma Concentration Curve From Time 0 to the Last Measurable Concentration (AUClast) for Carfilzomib

Pharmacokinetic analyses were conducted on a subset of participants at selected sites. Results are reported for participants in the PK analysis population with available data at each time point. PK profiles with a coefficient of determination (R²; goodness of fit) \< 0.8 or percent extrapolated AUC \> 20% were excluded from the analysis.

Area Under the Plasma Concentration Curve From Time 0 Extrapolated to Infinity (AUC0-inf) for Carfilzomib

Terminal Elimination Half-Life (T½) for Carfilzomib

Systemic Clearance (CL) of Carfilzomib After Intravenous Infusion

Volume of Distribution (Varea) of Carfilzomib

PK analyses were conducted on a subset of participants at selected sites. Results are reported for participants in the PK analysis population with available data at each time point. PK profiles with a coefficient of determination \< 0.8, percent extrapolated AUC \> 20%, or negative values for Vss were excluded from the analysis.

Volume of Distribution at Steady State (Vss) for Carfilzomib

PK analyses were conducted on a subset of participants at selected sites. Results are reported for the participants in PK analysis population with available data at each time point. PK profiles with a coefficient of determination \< 0.8, percent extrapolated AUC \> 20%, or negative values for MRT were excluded from the analysis.

Spots Global Cancer Trial Database for Carfilzomib in Combination With Dexamethasone (Kd) in Chinese Patients With Relapsed & Refractory Multiple Myeloma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

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