Multiple MyelomaPhase 1NCT02335983

Phase 1b Study of Weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma

A Phase 1 study testing Carfilzomib, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Amgen at 59 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Multiple Myeloma
What is being tested?: Carfilzomib, Lenalidomide and Dexamethasone
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 107 participants
Where: 59 sitesUnited States
Study dates: 30 Apr 2015to 28 Oct 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Newly diagnosed or relapsed multiple myeloma
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).
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2
Left ventricular ejection fraction (LVEF) ≥ 40%

Who cannot join

Waldenström macroglobulinemia
For newly diagnosed multiple myeloma: multiple myeloma of IgM subtype
For relapsed disease:
If treated with a lenalidomide and dexamethasone combination, progression during the first 3 months after initiating treatment.
Any progression during treatment if the lenalidomide and dexamethasone regimen was the most recent line of therapy.
Any prior treatment with carfilzomib

Show all 11Show fewer

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
Myelodysplastic syndrome
Amyloidosis
Prior treatment with carfilzomib or oprozomib

Trial locations and contacts

59 sites in 1 country.

City, postcode or hospital

59 sites in 1 country

United States59 sites

Research Site
Ann Arbor, Michigan, 48109
Research Site
Aurora, Colorado, 80045
University of Colorado
Aurora, Colorado
Research Site
Bakersfield, California, 93309
CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
Bakersfield, California
Research Site
Bend, Oregon, 97701
Bend Memorial Clinic
Bend, Oregon
Research Site
Boston, Massachusetts, 02114
Dana Farber Partners Cancer Care
Boston, Massachusetts
Research Site
Burbank, California, 91505
Providence Saint Joseph Medical Center
Burbank, California
Research Site
Charleston, South Carolina, 29424
Medical University of South Carolina, Hollings Cancer Center
Charleston, South Carolina
University of Chicago Medical Center
Chicago, Illinois
Research Site
Cincinnati, Ohio, 45242
Sarah Cannon Research Institute
Cincinnati, Ohio
Research Site
Durham, North Carolina, 27705
Durham Veterans Affairs Medical Center
Durham, North Carolina
Research Site
Fort Myers, Florida, 33905
Florida Cancer Specialists
Fort Myers, Florida
Research Site
Fountain Valley, California, 92708
Compassionate Care Research Group, Inc.
Fountain Valley, California
Research Site
Germantown, Tennessee, 38138
Research Site
Greenville, South Carolina, 29607
Greenville Health System
Greenville, South Carolina
Saint Francis Hospital Cancer Center
Greenville, South Carolina
Research Site
Hackensack, New Jersey, 07601
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey
Research Site
Los Angeles, California, 90017
Research Site
Los Angeles, California, 90095-1686
Los Angeles Hematology / Oncology Medical Group
Los Angeles, California
The West Clinic, PC
Memphis, Tennessee
Aurora Health Care, Aurora Cancer Care
Milwaukee, Wisconsin
Research Site
Nashville, Tennessee, 37203
Research Site
Nashville, Tennessee, 37232
Tennessee Oncology, PLLC / The Sarah Cannon Research lnstitute
Nashville, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee
Research Site
New York, New York, 10021
Research Site
New York, New York, 10065
Clinical Research Alliance
New York, New York
Memorial Sloan Kettering
New York, New York
Morton Coleman, MD
New York, New York
Weill Cornell Medical College
New York, New York
Research Site
Salt Lake City, Utah, 84112
Huntsman Cancer Institute
Salt Lake City, Utah
Research Site
Seattle, Washington, 98104
Swedish Cancer Institute
Seattle, Washington
Research Site
Sioux Falls, South Dakota, 57105
Avera Cancer Institute
Sioux Falls, South Dakota
Research Site
Stony Brook, New York, 11794
Stony Brook University Medical Center
Stony Brook, New York
Research Site
Tampa, Florida, 33612
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida
Research Site
Washington D.C., District of Columbia, 20057
Lombardi Cancer Center, Pediatric Hematology Oncology
Washington D.C., District of Columbia
Research Site
Wauwatosa, Wisconsin, 53226
Research Site
West Palm Beach, Florida, 33401
Florida Cancer Specialists
West Palm Beach, Florida
Research Site
Whittier, California, 90603

Other trials in United States

About this study

Official title: Phase 1b Study of Carfilzomib Administered Once Weekly in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma

Conditions: Multiple Myeloma
Being tested: Carfilzomib, Lenalidomide, Dexamethasone
Medical subject headings: Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CarfilzomibDrug
Also called PR-171, PR171, Kyprolis® (carfilzomib) for Injection
Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.
LenalidomideDrug
Also called Revlimid®
Administered orally once daily on days 1-21 of each 28-day cycle.
DexamethasoneDrug
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.

Study groups in NCT02335983
Study group	Role	What they receive
RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Experimental	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. Receives: Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone
RRMM Dose-evaluation: Carfilzomib 70 mg/m²	Experimental	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. Receives: Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone
RRMM Dose-expansion: Carfilzomib 70 mg/m²	Experimental	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. Receives: Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone
NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²	Experimental	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. Receives: Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone
NDMM Dose-expansion: Carfilzomib 70 mg/m²	Experimental	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. Receives: Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone
NDMM Dose-expansion: Carfilzomib 56 mg/m²	Experimental	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. Receives: Drug: Carfilzomib; Drug: Lenalidomide; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Adverse Events (AEs)
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.
Measured: 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.
Change From Baseline in Hemoglobin Levels
Measured: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Change From Baseline in Platelet Count
Measured: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Change From Baseline in Neutrophil Count
Measured: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Change From Baseline in Bilirubin
Measured: Baseline and Cycle 2 day 1
Change From Baseline in Creatinine
Measured: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15

Secondary outcomes (7)

Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Measured: 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
Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Measured: 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
Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Measured: 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
Overall Response Rate (ORR)
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.
Measured: 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.
Complete Response Rate (CRR)
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.
Measured: 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.
Progression-free Survival (PFS)
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.
Measured: 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.
Duration of Response (DOR)
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.
Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

30 Apr 201528 Oct 2019

First posted12 Jan 2015 (estimated)
Study start30 Apr 2015
Primary completion28 Oct 2019
Study completion28 Oct 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Multiple MyelomaStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 107 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02335983
Sponsor's protocol ID: CFZ013
Status last verified: Sep 2020
First submitted: 23 Dec 2014
Last updated: 6 Nov 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Publications

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.
PubMed 31021005

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
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All Multiple Myeloma trials

Study at a glance

From the registry record, last updated by the sponsor on 6 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase 1b Study of Carfilzomib Administered Once Weekly in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma
ClinicalTrials.gov ID: NCT02335983
Acronym / sponsor ID: CFZ013
Conditions: Multiple Myeloma
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 107 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 30 Apr 2015 (actual)
Primary completion: 28 Oct 2019 (actual)
Study completion: 28 Oct 2019 (actual)
First posted: 12 Jan 2015 (estimated)
Results: Posted 6 Nov 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
RRMM Dose-evaluation: Carfilzomib 56 mg/m²	Experimental	Drug: Carfilzomib, Drug: Lenalidomide, Drug: DexamethasoneParticipants 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.
RRMM Dose-evaluation: Carfilzomib 70 mg/m²	Experimental	Drug: Carfilzomib, Drug: Lenalidomide, Drug: DexamethasoneParticipants 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.
RRMM Dose-expansion: Carfilzomib 70 mg/m²	Experimental	Drug: Carfilzomib, Drug: Lenalidomide, Drug: DexamethasoneParticipants 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.
NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²	Experimental	Drug: Carfilzomib, Drug: Lenalidomide, Drug: DexamethasoneParticipants 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.
NDMM Dose-expansion: Carfilzomib 70 mg/m²	Experimental	Drug: Carfilzomib, Drug: Lenalidomide, Drug: DexamethasoneParticipants 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.
NDMM Dose-expansion: Carfilzomib 56 mg/m²	Experimental	Drug: Carfilzomib, Drug: Lenalidomide, Drug: DexamethasoneParticipants 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Newly diagnosed or relapsed multiple myeloma
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).
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2
Left ventricular ejection fraction (LVEF) ≥ 40%

Key exclusion criteria (11 listed)

Waldenström macroglobulinemia
For newly diagnosed multiple myeloma: multiple myeloma of IgM subtype
For relapsed disease:
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CarfilzomibAlso: PR-171, PR171, Kyprolis® (carfilzomib) for InjectionAdministered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.	Drug	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
LenalidomideAlso: Revlimid®Administered orally once daily on days 1-21 of each 28-day cycle.	Drug	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
DexamethasoneAdministered 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.	Drug	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

Primary outcome

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.
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.
Change From Baseline in Hemoglobin Levels
Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Change From Baseline in Platelet Count
Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Change From Baseline in Neutrophil Count
Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
Change From Baseline in Bilirubin
Time frame: Baseline and Cycle 2 day 1
Change From Baseline in Creatinine
Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15

7 secondary outcomes

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
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
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
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.
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.
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.
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.

Results and safety

Results posted to the registry on 6 Nov 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
RRMM Dose-evaluation: Carfilzomib 56 mg/m²	10	2
RRMM Dose-evaluation: Carfilzomib 70 mg/m²	12	3
RRMM Dose-expansion: Carfilzomib 70 mg/m²	34	2
NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²	9	0
NDMM Dose-expansion: Carfilzomib 70 mg/m²	9	1
NDMM Dose-expansion: Carfilzomib 56 mg/m²	33	1

Primary outcome: 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.. Count of participants. Unit: Participants

Measure	RRMM Dose-evaluation: Carfilzomib 56 mg/m² n = 10	RRMM Dose-evaluation: Carfilzomib 70 mg/m² n = 12	RRMM Dose-expansion: Carfilzomib 70 mg/m² n = 34	NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² n = 9	NDMM Dose-expansion: Carfilzomib 70 mg/m² n = 9	NDMM Dose-expansion: Carfilzomib 56 mg/m² n = 33
Any adverse event (AE)	10	12	34	9	9	33
AE Grade ≥ 3	7	9	23	5	6	21
Serious adverse events	4	5	10	3	3	11
AEs leading to discontinuation of carfilzomib	1	2	5	0	2	1
AEs leading to discontinuation of lenalidomide	1	2	5	0	2	2
AEs leading to discontinuation of dexamethasone	1	2	5	0	2	2
Fatal adverse events	0	0	2	0	0	0
Treatment-related adverse events (TRAE)	9	11	30	9	9	32

Population analysed: All participants who received at least 1 dose of study drug (safety analysis set).

Primary outcome: Change From Baseline in Hemoglobin Levels

Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15. Mean (Standard Deviation). Unit: g/L

Measure	RRMM Dose-evaluation: Carfilzomib 56 mg/m² n = 10	RRMM Dose-evaluation: Carfilzomib 70 mg/m² n = 12	RRMM Dose-expansion: Carfilzomib 70 mg/m² n = 34	NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² n = 8	NDMM Dose-expansion: Carfilzomib 70 mg/m² n = 9	NDMM Dose-expansion: Carfilzomib 56 mg/m² n = 33
Baseline	116.90 (14.58)	120.67 (13.51)	123.24 (16.57)	111.50 (18.04)	120.00 (20.96)	113.21 (16.66)
Change from Baseline to Cycle 1 Day 8	-1.50 (7.52)	-3.33 (6.39)	-0.91 (5.46)	-1.25 (8.17)	-5.56 (6.11)	-1.82 (7.21)
Change from Baseline to Cycle 1 Day 15	-6.90 (8.61)	-9.50 (6.29)	-5.10 (7.88)	-1.75 (12.70)	-6.50 (10.20)	-5.64 (9.10)
Change from Baseline to Cycle 2 Day 1	-5.70 (9.78)	-9.25 (8.67)	-7.38 (7.76)	-3.75 (12.65)	-3.29 (9.60)	2.19 (10.59)
Change from Baseline to Cycle 2 Day 8	-6.00 (11.91)	-8.17 (9.00)	-5.59 (8.35)	-0.13 (14.64)	-2.86 (8.49)	4.19 (12.41)
Change from Baseline to Cycle 2 Day 15	-8.50 (12.47)	-11.33 (8.04)	-8.45 (10.08)	0.00 (14.05)	-5.14 (13.58)	2.97 (13.04)

Population analysed: Participants in the safety analysis set with available data at Baseline and each time point.

Primary outcome: Change From Baseline in Platelet Count

Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15. Mean (Standard Deviation). Unit: 10^9 cells/L

Measure	RRMM Dose-evaluation: Carfilzomib 56 mg/m² n = 10	RRMM Dose-evaluation: Carfilzomib 70 mg/m² n = 12	RRMM Dose-expansion: Carfilzomib 70 mg/m² n = 34	NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² n = 8	NDMM Dose-expansion: Carfilzomib 70 mg/m² n = 9	NDMM Dose-expansion: Carfilzomib 56 mg/m² n = 33
Baseline	151.60 (54.40)	202.50 (67.13)	172.38 (33.70)	214.00 (79.22)	242.89 (99.24)	233.03 (67.76)
Change from Baseline to Cycle 1 Day 8	-12.90 (29.88)	-49.50 (58.90)	-17.36 (21.75)	2.38 (63.66)	-51.11 (42.10)	-21.42 (36.40)
Change from Baseline to Cycle 1 Day 15	-58.60 (32.76)	-66.83 (87.14)	-66.39 (38.30)	-23.25 (116.67)	-101.88 (84.66)	-53.39 (43.60)
Change from Baseline to Cycle 2 Day 1	55.00 (38.61)	68.67 (84.62)	44.84 (52.82)	141.75 (92.68)	152.00 (244.50)	111.06 (84.26)
Change from Baseline to Cycle 2 Day 8	-44.10 (38.14)	-74.75 (86.91)	-71.06 (37.93)	-28.00 (111.10)	-106.29 (130.18)	-52.78 (60.70)
Change from Baseline to Cycle 2 Day 15	-44.40 (21.48)	-63.25 (72.53)	-60.13 (43.37)	-21.25 (82.11)	-76.14 (116.02)	-44.19 (64.73)

Population analysed: Participants in the safety analysis set with available data at Baseline and each time point.

Primary outcome: Change From Baseline in Neutrophil Count

Time frame: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15. Mean (Standard Deviation). Unit: 10^9 cells/L

Measure	RRMM Dose-evaluation: Carfilzomib 56 mg/m² n = 10	RRMM Dose-evaluation: Carfilzomib 70 mg/m² n = 12	RRMM Dose-expansion: Carfilzomib 70 mg/m² n = 34	NDMM Dose-evaluation: Carfilzomib 56/70 mg/m² n = 8	NDMM Dose-expansion: Carfilzomib 70 mg/m² n = 9	NDMM Dose-expansion: Carfilzomib 56 mg/m² n = 33
Baseline	2.53 (1.01)	3.40 (1.54)	2.72 (0.94)	3.04 (0.73)	3.24 (2.24)	3.26 (1.46)
Change from Baseline to Cycle 1 Day 8	0.02 (0.82)	0.03 (1.87)	0.97 (1.19)	0.59 (1.20)	-0.19 (1.25)	0.37 (1.29)
Change from Baseline to Cycle 1 Day 15	0.28 (1.14)	-0.09 (1.94)	0.81 (1.09)	1.08 (1.53)	0.43 (1.83)	0.09 (1.48)
Change from Baseline to Cycle 2 Day 1	0.36 (1.99)	-0.33 (1.59)	0.16 (1.15)	0.02 (0.58)	0.09 (2.46)	0.18 (0.95)
Change from Baseline to Cycle 2 Day 8	0.18 (0.68)	-0.67 (1.28)	0.63 (1.08)	0.57 (1.05)	0.46 (2.49)	0.41 (1.25)
Change from Baseline to Cycle 2 Day 15	-0.30 (0.71)	-0.54 (1.69)	-0.06 (1.25)	0.33 (0.53)	0.56 (2.92)	0.42 (2.00)

Population analysed: Participants in the safety analysis set with available data at each time point.

7 secondary outcomes are reported in the full results.

Adverse events

Time frame: All-cause Mortality is reported from the enrollment date up to the end of study; maximum time on study was 30.6 months. Treatment-emergent adverse events are reported 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.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
RRMM Dose-evaluation: Carfilzomib 56 mg/m²	4 of 10 (40%)	10 of 10 (100%)	0 of 10
RRMM Dose-evaluation: Carfilzomib 70 mg/m²	5 of 12 (41.7%)	12 of 12 (100%)	0 of 12
RRMM Dose-expansion: Carfilzomib 70 mg/m²	10 of 34 (29.4%)	33 of 34 (97.1%)	2 of 34
NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²	3 of 9 (33.3%)	9 of 9 (100%)	0 of 9
NDMM Dose-expansion: Carfilzomib 70 mg/m²	3 of 9 (33.3%)	9 of 9 (100%)	0 of 9
NDMM Dose-expansion: Carfilzomib 56 mg/m²	11 of 33 (33.3%)	33 of 33 (100%)	0 of 33

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 31021005Biran 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.
AmgenTrials clinical trials websiteLink provided by the sponsor.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Amy Kimball, MD study director

Amgen

59 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Carfilzomib, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Amgen at 59 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 59 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02335983, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2020.