NCT02335983 · REGISTRY CONDITION SEARCH

Phase 1b Study of Weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With 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: PHASE1
Status at capture: COMPLETED
Registry last update: 2020-11-06

The purpose of the study is to assess the safety, tolerability and activity of a once-weekly regimen of carfilzomib in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma.

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

Number of Participants With Adverse Events (AEs)

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outcome · POSTED

Change From Baseline in Hemoglobin Levels

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outcome · POSTED

Change From Baseline in Platelet Count

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outcome · POSTED

Change From Baseline in Neutrophil Count

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outcome · POSTED

Change From Baseline in Bilirubin

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outcome · POSTED

Change From Baseline in Creatinine

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outcome · POSTED

Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group

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outcome · POSTED

Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group

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outcome · POSTED

Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group

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outcome · POSTED

Overall Response Rate (ORR)

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outcome · POSTED

Complete Response Rate (CRR)

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outcome · POSTED

Progression-free Survival (PFS)

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outcome · POSTED

Duration of Response (DOR)

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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: Key Inclusion Criteria: 1. Newly diagnosed or relapsed multiple myeloma 2. Measureable disease by serum M protein, or urine M protein, or serum free light chain (SFLC) and an abnormal serum kappa lambda ratio (for subjects without detectable serum or urine M-protein), or serum quantitative immunoglobulin A (glgA) (for immunoglobulin (Ig) A subjects whose disease can only be reliable measured by qlgA). 3. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2 4. Left ventricular ejection fraction (LVEF) ≥ 40% Key Exclusion Criteria: 1. Waldenström macroglobulinemia 2. For newly diagnosed multiple myeloma: multiple myeloma of IgM subtype 3. For relapsed disease: 1. If treated with a lenalidomide and dexamethasone combination, progression during the first 3 months after initiating treatment. 2. Any progression during treatment if the lenalidomide and dexamethasone regimen was the most recent line of therapy. 3. Any prior treatment with carfilzomib 4. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) 5. Plasma cell leukemia (\> 2.0 × 10\^9/L circulating plasma cells by standard differential) 6. Myelodysplastic syndrome 7. Amyloidosis 8. Prior treatment with carfilzomib or oprozomib
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
intervention Names
Drug: Carfilzomib
Drug: Lenalidomide
Drug: Dexamethasone
label
RRMM Dose-evaluation: Carfilzomib 56 mg/m²
type
EXPERIMENTAL
description
Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
intervention Names
Drug: Carfilzomib
Drug: Lenalidomide
Drug: Dexamethasone
label
RRMM Dose-evaluation: Carfilzomib 70 mg/m²
type
EXPERIMENTAL
description
Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
intervention Names
Drug: Carfilzomib
Drug: Lenalidomide
Drug: Dexamethasone
label
RRMM Dose-expansion: Carfilzomib 70 mg/m²
type
EXPERIMENTAL
description
Participants with newly diagnosed multiple myeloma (NDMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1 day 1, 56 mg/m² on cycle 1 days 8 and 15, and then 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
intervention Names
Drug: Carfilzomib
Drug: Lenalidomide
Drug: Dexamethasone
label
NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²
type
EXPERIMENTAL
description
Participants with NDMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
intervention Names
Drug: Carfilzomib
Drug: Lenalidomide
Drug: Dexamethasone
label
NDMM Dose-expansion: Carfilzomib 70 mg/m²
type
EXPERIMENTAL
description
Participants with NDMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8.
intervention Names
Drug: Carfilzomib
Drug: Lenalidomide
Drug: Dexamethasone
label
NDMM Dose-expansion: Carfilzomib 56 mg/m²
type
EXPERIMENTAL

interventions

arm Group Labels
NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²
NDMM Dose-expansion: Carfilzomib 56 mg/m²
NDMM Dose-expansion: Carfilzomib 70 mg/m²
RRMM Dose-evaluation: Carfilzomib 56 mg/m²
RRMM Dose-evaluation: Carfilzomib 70 mg/m²
RRMM Dose-expansion: Carfilzomib 70 mg/m²
description
Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.
name
Carfilzomib
other Names
PR-171
PR171
Kyprolis® (carfilzomib) for Injection
type
DRUG
arm Group Labels
NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²
NDMM Dose-expansion: Carfilzomib 56 mg/m²
NDMM Dose-expansion: Carfilzomib 70 mg/m²
RRMM Dose-evaluation: Carfilzomib 56 mg/m²
RRMM Dose-evaluation: Carfilzomib 70 mg/m²
RRMM Dose-expansion: Carfilzomib 70 mg/m²
description
Administered orally once daily on days 1-21 of each 28-day cycle.
name
Lenalidomide
other Names
Revlimid®
type
DRUG
arm Group Labels
NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²
NDMM Dose-expansion: Carfilzomib 56 mg/m²
NDMM Dose-expansion: Carfilzomib 70 mg/m²
RRMM Dose-evaluation: Carfilzomib 56 mg/m²
RRMM Dose-evaluation: Carfilzomib 70 mg/m²
RRMM Dose-expansion: Carfilzomib 70 mg/m²
description
Administered by mouth or IV at 40 mg on days 1, 8, and 15 of each 28-day cycle and on day 22 of cycles 1 to 8.
name
Dexamethasone
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 107
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Safety and tolerability were evaluated according to the type, incidence, and severity of adverse events. An AE is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria: * fatal * life threatening * requires in-patient hospitalization or prolongation of existing hospitalization * results in persistent or significant disability/incapacity * congenital anomaly/birth defect * other medically important serious event The severity of each AE was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.
measure
Number of Participants With Adverse Events (AEs)
time Frame
From the first dose of any study drug up to 30 days after the last dose of any study drug; median (range) duration of treatment with carfilzomib was 32 (1.1, 76.7) weeks in RRMM participants and 26 (1.0, 94.4) weeks in NDMM participants.
measure
Change From Baseline in Hemoglobin Levels
time Frame
Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
measure
Change From Baseline in Platelet Count
time Frame
Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
measure
Change From Baseline in Neutrophil Count
time Frame
Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
measure
Change From Baseline in Bilirubin
time Frame
Baseline and Cycle 2 day 1
measure
Change From Baseline in Creatinine
time Frame
Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15

secondary Outcomes

measure
Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
time Frame
Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
measure
Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
time Frame
Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
measure
Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
time Frame
Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
description
Response was determined by the investigator based on the International Myeloma Working Group Uniform Response Criteria (IMWG URC). ORR was defined as the percentage of participants who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Responses must have been confirmed in 2 consecutive assessments at any time prior to initiation of any new therapy. Disease assessments included serum protein electrophoresis (SPEP) with immunofixation, urine protein electrophoresis (UPEP; 24-hour assessment) with immunofixation, serum free light chain (SFLC), quantitative immunoglobulins, bone marrow aspirates to determine percent plasma cell involvement, and skeletal imaging for plasmacytoma evaluation.
measure
Overall Response Rate (ORR)
time Frame
Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
description
Complete Response Rate (CRR) is defined as the percentage of participants who achieved a best overall response of either stringent complete response (sCR) or complete response (CR) in accordance with International Myeloma Working Group-Uniform Response Criteria (IMWG-URC). sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM) CR: Negative serum and urine immunofixation, disappearance of any soft tissue plasmacytomas, \< 5% plasma cells in BM, and normal SFLC ratio in participants with measurable disease only by SFLC.
measure
Complete Response Rate (CRR)
time Frame
Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
description
PFS is defined as the time from the first day of study treatment to the earlier of disease progression or death due to any cause. Disease progression was determined by the investigator according to IMWG-URC. Progressive Disease (PD): Increase of 25% from lowest value in serum M-component (absolute increase ≥ 0.5 g/dL), urine M-component (absolute increase ≥ 200 mg per 24 hours) and/or the difference between involved and uninvolved FLC levels (absolute increase \>10 mg/dL) in patients without measurable serum and urine M-protein levels, and/or any new or increase in size of bone lesions or soft tissue plasmacytomas, or development of hypercalcemia. PFS was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after \> 1 consecutively missed assessment visit, were lost to follow-up or withdrew consent were censored at the date of last disease assessment.
measure
Progression-free Survival (PFS)
time Frame
From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
description
Duration of response (DOR) was calculated for participants who achieved a confirmed PR or better based on Investigator assessment and according to the IMWG URC. Duration of overall response is defined as the time from first documentation of response to disease progression or death due to any cause. DOR was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after \> 1 consecutively missed disease assessment visit, were lost to follow-up, or withdrew consent were censored at the date of last disease assessment.
measure
Duration of Response (DOR)
time Frame
From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.

Full study description

brief Summary: The purpose of the study is to assess the safety, tolerability and activity of a once-weekly regimen of carfilzomib in combination with lenalidomide and dexamethasone for the treatment of multiple myeloma.

Source references

references

citation
Biran N, Siegel D, Berdeja JG, Raje N, Cornell RF, Alsina M, Kovacsovics T, Fang B, Kimball AS, Landgren O. Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A phase 1b study. Am J Hematol. 2019 Jul;94(7):794-802. doi: 10.1002/ajh.25498. Epub 2019 May 13.
pmid
31021005
type
BACKGROUND