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Trial record 12 of 183 for:    carfilzomib OR pr-171

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

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ClinicalTrials.gov Identifier: NCT03029234
Recruitment Status : Active, not recruiting
First Posted : January 24, 2017
Last Update Posted : November 14, 2018
Sponsor:
Collaborator:
Onyx Therapeutics, Inc.
Information provided by (Responsible Party):
Amgen

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Relapsed and Refractory Multiple Myeloma Drug: Dexamethasone Drug: Carfilzomib Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 126 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Single-arm, Phase 3 Study of Carfilzomib in Combination With Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma in China
Actual Study Start Date : March 31, 2017
Actual Primary Completion Date : November 5, 2018
Estimated Study Completion Date : June 3, 2021


Arm Intervention/treatment
Experimental: Carfilzomib with Dexamethasone
On Cycle 1, Days 1 and 2, subjects will receive carfilzomib 20mg/m2. If tolerated (defined as absence of any treatment-related adverse event [AE] requiring dose reduction, delay, or the dose to be held), the dose will be escalated to 27 mg/m2 on Cycle 1 Day 8 and all subsequent doses.
Drug: Dexamethasone
20 mg intravenous (IV) or oral dexamethasone on Days 1, 2, 8, 9, 15, 16, 22, and 23 in 28-day Cycles.

Drug: Carfilzomib
Infusion of intravenous (IV) carfilzomib on Days 1, 2, 8, 9, 15 and 16. On Cycle 1, Days 1 and 2, subjects will receive carfilzomib 20 mg/m2. If tolerated (defined as absence of any treatment-related adverse event [AE] requiring dose reduction, delay, or the dose to be held), the dose will be escalated to 27 mg/m2 on Cycle 1 Day 8 and all subsequent doses.
Other Name: Kyprolis




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 6 cycles (28-day cycles) ]
    Overall Response Rate (ORR) will be determined after at least 6 cycles of Kd based on best response assessed by the IRC


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 6 cycles (28-day cycles) ]
    Overall Response Rate (ORR) will be determined after at least 6 cycles of Kd based on best response assessment by the investigator

  2. Overall Response Rate (ORR) [ Time Frame: 12 cycles (28-day cycles) ]
    Overall Response Rate (ORR) will be determined after at least 12 cycles of Kd based on both investigator and IRC assessment of best response

  3. Clinical Benefit Rate (CBR) [ Time Frame: 6 cycles (28-day cycles) ]
    Clinical Benefit Rate (CBR) will be determined using investigator assessment of response.

  4. Clinical Benefit Rate (CBR) [ Time Frame: 12 cycles (28-day cycles) ]
    Clinical Benefit Rate (CBR) will be determined using investigator assessment of response.

  5. Duration of Response (DOR) [ Time Frame: Approximately 4 years after first subject enrolled ]
    The time from first evidence of PR or better to disease progression or death due to any cause based on both investigator and IRC response assessments

  6. Duration of Clinical Benefit (DCB) [ Time Frame: Approximately 4 years after first subject enrolled ]
    The time from first evidence of MR or better to disease progression or death due to any cause based on both investigator and IRC response assessments. Analysis will be performed using the Kaplan-Meier method.

  7. Progression-Free Survival (PFS) [ Time Frame: Approximately 4 years after first subject enrolled ]
    The time from first dose to the earlier of disease progression or death due to any cause based on both investigator and IRC response assessments

  8. Overall Survival (OS) [ Time Frame: Approximately 4 years after first subject enrolled ]
    The time from first dose to the date of death (due to any cause)

  9. Time to Response (TTR) [ Time Frame: Approximately 4 years after first subject enrolled ]
    The time from the start of study treatment until the start of first confirmed response (PR or better) based on both investigator and IRC response assessments

  10. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Cycle 1 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  11. Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Cycle 2 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  12. Area Under the Plasma Concentration Curve Up to the Last Measurable Concentration (AUClast) [ Time Frame: Cycle 1 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  13. Area Under the Plasma Concentration Curve Up to the Last Measurable Concentration (AUClast) [ Time Frame: Cycle 2 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  14. Area Under the Plasma Concentration Curve Extrapolated to Infinity (AUC0-inf) [ Time Frame: Cycle 1 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  15. Area Under the Plasma Concentration Curve Extrapolated to Infinity (AUC0-inf) [ Time Frame: Cycle 2 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  16. Time to Maximum Concentration (Tmax) [ Time Frame: Cycle 1 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  17. Time to Maximum Concentration (Tmax) [ Time Frame: Cycle 2 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  18. Terminal Elimination Half Half-Life (T½) [ Time Frame: Cycle 1 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  19. Terminal Elimination Half Half-Life (T½) [ Time Frame: Cycle 2 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  20. Total Plasma Clearance (CL) [ Time Frame: Cycle 1 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  21. Total Plasma Clearance (CL) [ Time Frame: Cycle 2 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  22. Volume of Distribution [Varea] [ Time Frame: Cycle 1 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  23. Volume of Distribution [Varea] [ Time Frame: Cycle 2 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  24. Volume of Distribution at Steady State [Vss] [ Time Frame: Cycle 1 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  25. Volume of Distribution at Steady State [Vss] [ Time Frame: Cycle 2 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  26. Mean Residence Time (MRT) [ Time Frame: Cycle 1 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects

  27. Mean Residence Time (MRT) [ Time Frame: Cycle 2 Day 1 ]
    To characterize pharmacokinetics (PK) in a subset of subjects


Other Outcome Measures:
  1. Overall Response Rate (ORR) [ Time Frame: 6 cycles (28-day cycles) ]
    Overall Response Rate (ORR) will be determined after at least 6 cycles of Kd based on Onyx Response Computational Assessment (ORCA) assessment of response

  2. Overall Response Rate (ORR) [ Time Frame: 12 cycles (28-day cycles) ]
    Overall Response Rate (ORR) will be determined after at least 12 cycles of Kd based on Onyx Response Computational Assessment (ORCA) assessment of response

  3. Clinical Benefit Rate (CBR) [ Time Frame: 6 cycles (28-day cycles) ]
    Clinical Benefit Rate (CBR) will be estimated using Onyx Response Computational Assessment (ORCA)

  4. Clinical Benefit Rate (CBR) [ Time Frame: 12 cycles (28-day cycles) ]
    Clinical Benefit Rate (CBR) will be estimated using Onyx Response Computational Assessment (ORCA)

  5. Duration of Response [ Time Frame: Approximately 4 years after first subject enrolled ]
    The time from first evidence of PR or better to disease progression or death due to any cause based on Onyx Response Computational Assessment (ORCA) estimate

  6. Duration of Clinical Benefit (DCB) [ Time Frame: Approximately 4 years after first subject enrolled ]
    The time from first evidence of MR or better to disease progression or death due to any cause based on Onyx Response Computational Assessment (ORCA) estimate

  7. Progression Free Survival (PFS) [ Time Frame: Approximately 4 years after first subject enrolled ]
    The time from first dose to the earlier of disease progression or death due to any cause based on Onyx Response Computational Assessment (ORCA) estimate

  8. Time to Response (TTR) [ Time Frame: Approximately 4 years after first subject enrolled ]
    The time from start of study treatment until the start of first confirmed response (PR or better) based on both based on Onyx Response Computational Assessment (ORCA) estimate



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Multiple myeloma
  • Subjects must have measurable disease, defined as one or more of the following:
  • Serum M-protein ≥ 1 g/dL
  • Urine M-protein ≥ 200 mg/24 hours
  • In subjects without measurable serum or urine M-protein, SFLC > 100 mg/L (involved light chain) and an abnormal κ/λ ratio
  • Subjects must have been responsive (ie, achieved a minimal response [MR] or better) to at least one of their prior treatment regimens
  • Refractory to the most recently received therapy. Refractory disease defined as ≤ 25% response to, or progressing during therapy or within 60 days after completion of therapy
  • Subjects must have received ≥ 2 prior regimens. Induction therapy and stem cell transplant (± maintenance) will be considered as 1 regimen
  • Subjects must have received prior treatment with bortezomib and an IMiD
  • Subjects must have received an alkylating agent or anthracycline alone or in combination with other myeloma treatments (this may include high dose melphalan as part of the conditioning regimen prior to a stem cell transplant)
  • Males and females ≥ 18 years of age
  • Life expectancy of more than 3 months
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
  • Adequate hepatic function, with bilirubin < 2.0 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.0 times the ULN
  • Absolute neutrophil count (ANC) ≥ 1,000/mm3, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 50,000/mm3

    • Subjects should not have received platelet transfusions for at least 1 week prior to obtaining the screening platelet count
    • Screening ANC should be independent of granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF) support for ≥ 1 week and pegylated G-CSF for ≥ 2 weeks
    • Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed; however, most recent RBC transfusion may not have been done within 7 days prior to obtaining screening hemoglobin
  • Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/min. Calculated CrCl should be performed by using a widely accepted equation (eg, the Cockcroft and Gault equation): ([140 - Age] × Mass [kg] / [72 × Creatinine mg/dL]). Multiply the result by 0.85 if the subject is female.
  • Left ventricular ejection fraction (LVEF) ≥ 40%; 2-dimensional transthoracic echocardiogram (ECHO) is the preferred method of evaluation; multiple gated acquisition scan (MUGA) is acceptable if ECHO is not available
  • Written informed consent in accordance with federal, local, and institutional guidelines
  • Female subjects of child-bearing potential (FCBP) must have a negative serum pregnancy test within 21 days prior to enrollment and agree to use an effective method of contraception during and for 30 days following last dose of carfilzomib. This protocol defines a FCBP as a sexually mature woman who: 1) has not undergone a hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, or 2) has not been naturally postmenopausal for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months)
  • Male subjects must use an effective barrier method of contraception during the study and for 3 months following the last dose of carfilzomib if sexually active with a FCBP. Male subjects must not donate sperm during treatment and for an additional 90 days after last dose of carfilzomib. Male subjects with pregnant partners must practice sexual abstinence or use a condom during vaginal sex

Exclusion Criteria:

  • Waldenström's macroglobulinemia or immunoglobulin M (IgM) multiple myeloma
  • Subjects who failed to achieve at least a confirmed MR on any of their prior regimens
  • Subjects with non-secretory multiple myeloma, defined as < 1 g/dL M-protein in serum and < 200 mg/24 hour M- protein in urine and SFLC ≤ 100 mg/L (involved light chain)
  • Glucocorticoid therapy (prednisone > 10 mg/day or equivalent) within 3 weeks prior to Cycle 1 Day 1
  • POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  • Plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard differential)
  • Chemotherapy with approved or investigative anticancer therapeutics including steroid therapy within the 3 weeks prior to Cycle 1 Day 1
  • Radiation therapy or immunotherapy in the 4 weeks prior to Cycle 1 Day 1; localized radiation therapy within 1 week prior to Cycle 1 Day 1
  • Participation in an investigational therapeutic study within 3 weeks or within 5 drug half-lives (T½) prior to Cycle 1 Day 1, whichever time is greater
  • Prior treatment with carfilzomib
  • Major surgery within 3 weeks before Cycle 1 Day 1
  • Congestive heart failure ([CHF] New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months prior to Cycle 1 Day 1
  • Uncontrolled hypertension (a sustained systolic blood pressure > 140 mmHg and/or diastolic BP > 90 mmHg)
  • Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to Cycle 1 Day 1
  • Known HIV seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B surface antigen or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed)
  • Non-hematologic malignancy within the past 3 years except:
  • Adequately treated basal cell or squamous cell skin cancer,
  • Carcinoma in situ of the cervix, or
  • Prostate cancer < Gleason Score 6 with stable prostate-specific antigen
  • Subjects with treatment-related myelodysplastic syndrome
  • Significant neuropathy (Grade 3, 4, or Grade 2 with pain) at the time of baseline evaluation
  • Subjects in whom the required program of PO or IV fluid hydration is contraindicated, eg, due to pre-existing pulmonary, cardiac, or renal impairment
  • Subjects with known or suspected amyloidosis
  • Subjects with pleural effusions requiring thoracentesis
  • Subjects with ascites requiring paracentesis
  • Any clinically significant medical disease or condition, that in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
  • Female subjects who are pregnant or lactating, or planning to become pregnant during treatment and for an additional 30 days after discontinuing carfilzomib.
  • Serious psychiatric or medical conditions that could interfere with treatment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03029234


Locations
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China, Beijing
Research Site
Beijing, Beijing, China, 100020
Research Site
Beijing, Beijing, China, 100191
China, Fujian
Research Site
Fuzhou, Fujian, China, 350001
China, Guangdong
Research Site
Guangzhou, Guangdong, China, 510060
Research Site
Guangzhou, Guangdong, China, 510180
China, Henan
Research Site
Zhengzhou, Henan, China, 450008
China, Hubei
Research Site
Wuhan, Hubei, China, 430014
China, Jiangsu
Research Site
Suzhou, Jiangsu, China, 215004
China, Jilin
Research Site
Changchun, Jilin, China, 130021
China, Liaoning
Research Site
Shenyang, Liaoning, China, 110001
China, Shanghai
Research Site
Shanghai, Shanghai, China, 200032
China, Sichuan
Research Site
Chengdu, Sichuan, China, 610041
China, Tianjin
Research Site
Tianjin, Tianjin, China, 300020
Research Site
Tianjin, Tianjin, China, 300052
China, Zhejiang
Research Site
Hangzhou, Zhejiang, China, 310003
China
Research Site
Beijing, China, 100730
Research Site
Shanghai, China, 200003
Sponsors and Collaborators
Amgen
Onyx Therapeutics, Inc.
Investigators
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Study Director: MD Amgen

Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03029234     History of Changes
Other Study ID Numbers: 20140242
First Posted: January 24, 2017    Key Record Dates
Last Update Posted: November 14, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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 link below.
URL: https://www.amgen.com/datasharing

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors