A Study of Carfilzomib Plus Dexamethasone in Adults With Relapsed or Refractory Multiple Myeloma at US Community Oncology Centers

NCT03512353 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 20170596
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 31

Brief Summary

The primary objective was to describe the safety profile of carfilzomib plus dexamethasone regimen in adults with relapsed or refractory multiple myeloma (RRMM) with 1 to 3 prior lines of therapy at study entry.

Conditions

Relapsed or Refractory Multiple Myeloma

Outcome Measures

Primary Outcomes (5)

• Number of Participants Who Completed 12 Cycles of Treatment

  12 cycles (each cycle is 28 days)

• Percentage of Expected Dose of Carfilzomib Received in Cycles 1 to 12

  Percentage of expected dose of carfilzomib is defined as the percentage of actual cumulative dose (mg/m²) received by the participant relative to the full intended cumulative dose (mg/m²).

  Up to 12 cycles (each cycle is 28 days)

• Relative Dose Intensity of Carfilzomib in Cycles 1 to 12

  Relative dose intensity = actual dose intensity / planned dose intensity \* 100, where dose intensity is the cumulative dose (mg) divided by the duration of the study drug administration (weeks).

  Up to 12 Cycles (each cycle is 28 days)

• Number of Participants With Carfilzomib Dose Modifications During Cycles 1 to 12

  Dose modification includes dosage adjustments, delays or discontinuations. A participant is counted only once for a reason category if there were multiple occurrences for the same reason. Participants may be counted in more than one category.

  Cycles 1 - 12 (each cycle is 28 days)

• Number of Participants With Treatment-emergent Adverse Events

  Treatment-emergent adverse events are defined as any adverse event with an onset date from the first dose through 30 days after the last dose of any study drug. Treatment-emergent related adverse events are adverse events considered related to at least one study drug by the investigator. Adverse events were graded using Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03, where Grade 1: Mild (asymptomatic or mild symptoms) Grade 2: Moderate (minimal, local or noninvasive intervention indicated) Grade 3: Severe (severe) or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated) Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE.

  From the first dose of study drug until 30 days after the last dose (12 months)

Secondary Outcomes (16)

• Percentage of Expected Dose of Carfilzomib Received in Cycles 1 to 6 and 7 to 12

  Cycles 1-6 and 7-12 (each cycle is 28 days)

• Relative Dose Intensity of Carfilzomib in Cycles 1 to 6 and 7 to 12

  Cycles 1 - 6 and 7 - 12 (each cycle is 28 days)

• Number of Participants With Carfilzomib Dose Modifications During Cycles 1 to 6

  Cycles 1 - 6 (each cycle is 28 days)

• Number of Participants With Carfilzomib Dose Modifications During Cycles 7 to 12

  Cycles 7 - 12 (each cycle is 28 days)

• Number of Participants Who Discontinued Carfilzomib in Cycles 1 to 6 and 7 to 12

  Cycles 1 - 6 and 7 - 12 (each cycle is 28 days)

Study Arms (1)

Carfilzomib Plus Dexamethasone

EXPERIMENTAL

Participants received carfilzomib administered as an intravenous (IV) infusion twice-weekly for up to six 28-day cycles followed by once-weekly for another six 28-day cycles. The carfilzomib dose was 20 mg/m² on days 1 and 2 of cycle 1, 56 mg/m² for the remaining days of cycle 1 (days 8, 9, 15, and 16) and then on days 1, 2, 8, 9, 15, and 16 of each cycle for cycles 2 to 6, and 70 mg/m² on days 1, 8, and 15 of each cycle for cycles 7 to 12. Participants also received dexamethasone either orally or by IV infusion at a dose of 20 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 of cycles 1 to 6 and at a dose 40 mg once daily on days 1, 8, 15 of cycles 7 to 12.

Drug: Dexamethasone; Drug: Carfilzomib

Interventions

Dexamethasone DRUG

Dexamethasone will be taken orally or by IV infusion at a dose of 20 mg once-daily on days 1, 2, 8, 9, 15, 16, 22, and 23 of cycles 1-6, and at a dose 40 mg once-daily on days 1, 8, 15 of cycles 7-12.

Carfilzomib Plus Dexamethasone

Carfilzomib DRUG

Carfilzomib will be administered at 20 mg/m² on days 1 and 2 of the first cycle. After that, carfilzomib will be administered at 56 mg/m² on days 8, 9, 15, and 16 of the first cycle, and then on days 1, 2, 8, 9, 15, and 16 on each 28-day cycle for the cycles 2 through 6. Starting with cycle 7 through cycle 12, carfilzomib will be administered at 70 mg/m² on days 1, 8, and 15 of each 28-day cycle. All

Also known as: Kyprolis®

Carfilzomib Plus Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has provided informed consent prior to initiation of any study specific activities/procedures.
• Males or females greater than or equal to 18 years of age.
• Relapsed MM after last treatment or refractory while receiving non-proteasome inhibitor therapy.
• Measurable disease with at least 1 of the following assessed within 21 days prior to enrollment:
• Immunoglobulin G (IgG) MM: serum monoclonal protein (M-protein) level ≥ 1.0 g/dL
• IgA, IgD, IgE multiple myeloma: serum M protein level ≥ 0.5 g/dL
• Urine M-protein ≥ 200 mg per 24 hours
• In subjects without measurable serum or urine M-protein, serum free light chain (SFLC) ≥ 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1.
• Subjects must have at least partial response (PR) to at least 1 line of prior therapy.
• Subjects must have received at least 1 but not more than 3 prior lines of therapy for MM (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy).
• Prior therapy with a proteasome inhibitor (PI) is allowed as long as the subject had at least a PR to most recent therapy with PI, was not removed due to toxicity (except for neuropathy), did not relapse within 60 days from discontinuation of PI, and will have at least a 6-month PI treatment-free interval from last dose received until enrollment. (Subjects may receive maintenance therapy with drugs that are not PI during this 6-month PI treatment-free interval).

You may not qualify if:

• Waldenström macroglobulinemia.
• Multiple myeloma of IgM subtype.
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
• History of plasma cell leukemia.
• Primary amyloidosis (patients with multiple myeloma with asymptomatic deposition of amyloid plaques found on biopsy would be eligible if all other criteria are met).
• Subjects with nephrotic range proteinuria (greater than or equal to 3 g albumin for 24 hours urine OR greater than or equal to 2 g albumin/1 g of creatinine on a random urine specimen).
• Myelodysplastic syndrome.
• History of other malignancy within the past 5 years, with the following exceptions:
• Malignancy treated with curative intent and with no known active disease present for greater than or equal to 3 years before enrollment and felt to be at low risk for recurrence by the treating physician.
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
• Adequately treated cervical carcinoma in situ without evidence of disease.
• Adequately treated breast ductal carcinoma in situ without evidence of disease.
• Prostatic intraepithelial neoplasia without evidence of prostate cancer.
• Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
• Treated medullary or papillary thyroid cancer.

Sponsors & Collaborators

• Amgen: lead

Study Sites (31)

Research Site

Palm Springs, California, 92262, United States

Location

Research Site

Riverside, California, 92501, United States

Location

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Glenwood Springs, Colorado, 81601, United States

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Boynton Beach, Florida, 33426, United States

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Orange City, Florida, 32763, United States

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Pensacola, Florida, 32504, United States

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Honolulu, Hawaii, 96813, United States

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River Forest, Illinois, 60305, United States

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Tinley Park, Illinois, 60487, United States

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Indianapolis, Indiana, 46260, United States

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Paducah, Kentucky, 42003, United States

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Bethesda, Maryland, 20817, United States

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Midland, Michigan, 48640, United States

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Jackson, Mississippi, 39202, United States

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Lincoln, Nebraska, 68506, United States

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Florham Park, New Jersey, 07932, United States

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Charlotte, North Carolina, 28204, United States

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Charlotte, North Carolina, 28207, United States

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Hendersonville, North Carolina, 28792, United States

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Pinehurst, North Carolina, 28374, United States

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Winston-Salem, North Carolina, 27103, United States

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Zanesville, Ohio, 43701, United States

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Charleston, South Carolina, 29414, United States

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Rock Hill, South Carolina, 29732, United States

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Corpus Christi, Texas, 78412, United States

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Fort Worth, Texas, 76104, United States

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Houston, Texas, 77057, United States

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Houston, Texas, 77090, United States

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Ogden, Utah, 84405, United States

Location

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Fredericksburg, Virginia, 22408, United States

Location

Research Site

Yakima, Washington, 98902, United States

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

Dexamethasone; carfilzomib

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Limitations and Caveats

Because of the limited sample size, no meaningful conclusions on the study objectives can be made.

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2018
• First Posted: April 30, 2018
• Study Start: July 5, 2018
• Primary Completion: January 16, 2020
• Study Completion: January 16, 2020
• Last Updated: January 8, 2021
• Results First Posted: January 8, 2021

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

US (31)