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

NCT ID: NCT02335983

Last Updated: 2020-11-06

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

107 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-04-30

Study Completion Date

2019-10-28

Brief Summary

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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.

Detailed Description

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Conditions

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Multiple Myeloma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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RRMM Dose-evaluation: Carfilzomib 56 mg/m²

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.

Group Type EXPERIMENTAL

Carfilzomib

Intervention Type DRUG

Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.

Lenalidomide

Intervention Type DRUG

Administered orally once daily on days 1-21 of each 28-day cycle.

Dexamethasone

Intervention Type DRUG

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.

RRMM Dose-evaluation: Carfilzomib 70 mg/m²

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.

Group Type EXPERIMENTAL

Carfilzomib

Intervention Type DRUG

Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.

Lenalidomide

Intervention Type DRUG

Administered orally once daily on days 1-21 of each 28-day cycle.

Dexamethasone

Intervention Type DRUG

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.

RRMM Dose-expansion: Carfilzomib 70 mg/m²

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.

Group Type EXPERIMENTAL

Carfilzomib

Intervention Type DRUG

Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.

Lenalidomide

Intervention Type DRUG

Administered orally once daily on days 1-21 of each 28-day cycle.

Dexamethasone

Intervention Type DRUG

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.

NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²

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.

Group Type EXPERIMENTAL

Carfilzomib

Intervention Type DRUG

Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.

Lenalidomide

Intervention Type DRUG

Administered orally once daily on days 1-21 of each 28-day cycle.

Dexamethasone

Intervention Type DRUG

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.

NDMM Dose-expansion: Carfilzomib 70 mg/m²

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.

Group Type EXPERIMENTAL

Carfilzomib

Intervention Type DRUG

Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.

Lenalidomide

Intervention Type DRUG

Administered orally once daily on days 1-21 of each 28-day cycle.

Dexamethasone

Intervention Type DRUG

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.

NDMM Dose-expansion: Carfilzomib 56 mg/m²

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.

Group Type EXPERIMENTAL

Carfilzomib

Intervention Type DRUG

Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.

Lenalidomide

Intervention Type DRUG

Administered orally once daily on days 1-21 of each 28-day cycle.

Dexamethasone

Intervention Type DRUG

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.

Interventions

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Carfilzomib

Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.

Intervention Type DRUG

Lenalidomide

Administered orally once daily on days 1-21 of each 28-day cycle.

Intervention Type DRUG

Dexamethasone

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.

Intervention Type DRUG

Other Intervention Names

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PR-171 PR171 Kyprolis® (carfilzomib) for Injection Revlimid®

Eligibility Criteria

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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%

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Amy Kimball, MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Research Site

Bakersfield, California, United States

Site Status

CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center

Bakersfield, California, United States

Site Status

Research Site

Burbank, California, United States

Site Status

Providence Saint Joseph Medical Center

Burbank, California, United States

Site Status

Research Site

Fountain Valley, California, United States

Site Status

Compassionate Care Research Group, Inc.

Fountain Valley, California, United States

Site Status

Research Site

Los Angeles, California, United States

Site Status

Research Site

Los Angeles, California, United States

Site Status

Los Angeles Hematology / Oncology Medical Group

Los Angeles, California, United States

Site Status

Research Site

Whittier, California, United States

Site Status

Research Site

Aurora, Colorado, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

Research Site

Washington D.C., District of Columbia, United States

Site Status

Lombardi Cancer Center, Pediatric Hematology Oncology

Washington D.C., District of Columbia, United States

Site Status

Research Site

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialists

Fort Myers, Florida, United States

Site Status

Research Site

Tampa, Florida, United States

Site Status

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, United States

Site Status

Research Site

West Palm Beach, Florida, United States

Site Status

Florida Cancer Specialists

West Palm Beach, Florida, United States

Site Status

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status

Research Site

Boston, Massachusetts, United States

Site Status

Dana Farber Partners Cancer Care

Boston, Massachusetts, United States

Site Status

Research Site

Ann Arbor, Michigan, United States

Site Status

Research Site

Hackensack, New Jersey, United States

Site Status

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Research Site

New York, New York, United States

Site Status

Research Site

New York, New York, United States

Site Status

Clinical Research Alliance

New York, New York, United States

Site Status

Memorial Sloan Kettering

New York, New York, United States

Site Status

Morton Coleman, MD

New York, New York, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

Research Site

Stony Brook, New York, United States

Site Status

Stony Brook University Medical Center

Stony Brook, New York, United States

Site Status

Research Site

Durham, North Carolina, United States

Site Status

Durham Veterans Affairs Medical Center

Durham, North Carolina, United States

Site Status

Research Site

Cincinnati, Ohio, United States

Site Status

Sarah Cannon Research Institute

Cincinnati, Ohio, United States

Site Status

Research Site

Bend, Oregon, United States

Site Status

Bend Memorial Clinic

Bend, Oregon, United States

Site Status

Research Site

Charleston, South Carolina, United States

Site Status

Medical University of South Carolina, Hollings Cancer Center

Charleston, South Carolina, United States

Site Status

Research Site

Greenville, South Carolina, United States

Site Status

Greenville Health System

Greenville, South Carolina, United States

Site Status

Saint Francis Hospital Cancer Center

Greenville, South Carolina, United States

Site Status

Research Site

Sioux Falls, South Dakota, United States

Site Status

Avera Cancer Institute

Sioux Falls, South Dakota, United States

Site Status

Research Site

Germantown, Tennessee, United States

Site Status

The West Clinic, PC

Memphis, Tennessee, United States

Site Status

Research Site

Nashville, Tennessee, United States

Site Status

Research Site

Nashville, Tennessee, United States

Site Status

Tennessee Oncology, PLLC / The Sarah Cannon Research lnstitute

Nashville, Tennessee, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Research Site

Salt Lake City, Utah, United States

Site Status

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Site Status

Research Site

Seattle, Washington, United States

Site Status

Swedish Cancer Institute

Seattle, Washington, United States

Site Status

Aurora Health Care, Aurora Cancer Care

Milwaukee, Wisconsin, United States

Site Status

Research Site

Wauwatosa, Wisconsin, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 31021005 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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CFZ013

Identifier Type: -

Identifier Source: org_study_id