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A Study in Subjects With Relapsed and Refractory Multiple Myeloma Receiving Carfilzomib in Combination With Dexamethasone, Comparing Once-weekly Versus Twice-weekly Carfilzomib Dosing (ARROW)

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ClinicalTrials.gov Identifier: NCT02412878
Recruitment Status : Active, not recruiting
First Posted : April 9, 2015
Last Update Posted : June 12, 2018
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
The purpose of the study is to compare once-weekly carfilzomib dosing in combination with dexamethasone to twice-weekly carfilzomib dosing in combination with dexamethasone in subjects with relapsed and refractory multiple myeloma, previously treated with bortezomib and an immunomodulatory agent (IMiD).

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

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 478 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-label, Phase 3 Study in Subjects With Relapsed and Refractory Multiple Myeloma Receiving Carfilzomib in Combination With Dexamethasone, Comparing Once-weekly Versus Twice-weekly Carfilzomib Dosing
Actual Study Start Date : September 30, 2015
Actual Primary Completion Date : June 15, 2017
Estimated Study Completion Date : December 20, 2019


Arm Intervention/treatment
Active Comparator: Arm A: Once-weekly Carfilzomib with Dexamethasone
  • Carfilzomib 20 mg/m2 - Study Day 1 (Cycle 1)
  • Carfilzomib 70 mg/m2 - Study Days 8 and 15 (Cycle 1), Study Days 1, 8, and 15 (Cycles 2+)
  • Dexamethasone 40 mg (IV or PO) Study Days 1, 8, and 15 (all Cycles)
  • Dexamethasone 40 mg (IV or PO) Study Day 22 (Cycle 1-9 only)
Drug: Carfilzomib
Other Names:
  • PR-171
  • PR171
  • Kyprolis® (carfilzomib) for Injection

Drug: Dexamethasone
Active Comparator: Arm B: Twice-weekly Carfilzomib with Dexamethasone
  • Carfilzomib 20 mg/m2 - Study Days 1 and 2 (Cycle 1)
  • Carfilzomib 27 mg/m2 - Study Days 8, 9, 15, and 16 (Cycle 1), Study Days

    1, 2, 8, 9, 15, and 16 (Cycles 2+)

  • Dexamethasone 40 mg (IV or PO) Study Days 1, 8, and 15 (all Cycles)
  • Dexamethasone 40 mg (IV or PO) Study Day 22 (Cycle 1-9 only)
Drug: Carfilzomib
Other Names:
  • PR-171
  • PR171
  • Kyprolis® (carfilzomib) for Injection

Drug: Dexamethasone



Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 19 months ]
    Overall Response Rate (ORR) is defined as the proportion of subjects who achieve a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) in accordance with International Myeloma Working Group-Uniform Response Criteria (IMWG-URC).

  2. Progression Free Survival (PFS) [ Time Frame: 19 months ]
    Progression Free Survival (PFS) is defined as the time in months from randomization to the earlier of disease progression or death due to any cause


Secondary Outcome Measures :
  1. Progression-Free Survival (PFS) [ Time Frame: 25 months ]
    Progression-free survival (PFS) is defined as the time from randomization to the earlier of disease progression or death due to any cause.

  2. Overall Survival (OS) [ Time Frame: 25 months ]
    Overall Survival (OS) is defined as the time from randomization to death due to any cause.

  3. Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 25 months ]
    Safety and tolerability will be assessed by the incidence and severity of Adverse Events (AEs).

  4. Laboratory Values [ Time Frame: 25 months ]
    For laboratory values, the baseline values and changes from baseline to the minimum, maximum, and last observed values will be summarized descriptively by visit. Laboratory test results will be graded using the NCI-CTCAE (version 4.03).

  5. Vital Signs [ Time Frame: 25 months ]
    Vital sign results will be summarized descriptively for baseline values and changes from baseline to the minimum, maximum, and last observed values.

  6. Electrocardiogram (ECG) QT-interval [ Time Frame: 25 months ]
    Twelve-lead electrocardiograms (ECGs) including corrected QT-interval (QTc; representing the corrected duration of ventricular electrical activity) will be performed locally.

  7. Pharmacokinetics (PK) Plasma Samples (Concentrations of carfilzomib) [ Time Frame: 17 months ]
    Concentrations of carfilzomib will be measured in plasma with a validated assay method.

  8. Overall Response Rate (ORR) [ Time Frame: 19 months ]
    Overall Response Rate (ORR) is defined as the proportion of subjects who achieve a best overall response of partial response (PR), very good partial response (VGPR), complete response (sCR), or stringent complete response (CR) in accordance with International Myeloma Working Group-Uniform Response Criteria (IMWG-URC).



Information from the National Library of Medicine

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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

Key Inclusion Criteria:

  1. Relapsed multiple myeloma
  2. Refractory multiple myeloma defined as meeting 1 or more of the following:

    • Nonresponsive to most recent therapy (stable disease only or PD while on treatment), or
    • Disease progression within 60 days of discontinuation from most recent therapy
  3. At least 2 but no more than 3 prior therapies for multiple myeloma
  4. Prior exposure to an immunomodulatory agent (IMiD)
  5. Prior exposure to a proteasome inhibitor (PI)
  6. Documented response of at least partial response (PR) to 1 line of prior therapy
  7. Measurable disease with at least 1 of the following assessed within the 21 days prior to randomization:

    • Serum M-protein ≥ 0.5 g/dL
    • Urine M-protein ≥ 200 mg/24 hours
    • In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal serum kappa lambda ratio
  8. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
  9. Left ventricular ejection fraction (LVEF) ≥ 40% within the 21 days prior to randomization
  10. Adequate organ and bone marrow function within the 21 days prior to randomization defined by:

    • Bilirubin < 1.5 times the upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the ULN
    • Absolute neutrophil count (ANC) ≥ 1000/mm3 (screening ANC should be independent of growth factor support for ≥ 1 week)
    • Hemoglobin ≥ 8.0 g/dL (Use of erythropoietic stimulating factors and red blood cell [RBC] transfusion per institutional guidelines is allowed, however the most recent RBC transfusion may not have been done within 7 days prior to obtaining screening hemoglobin.)
    • Platelet count ≥ 50,000/mm3 (≥ 30,000/mm3 if myeloma involvement in the bone marrow is > 50%. Subjects should not have received platelet transfusions for at least 1 week prior to obtaining the screening platelet count.)
    • Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/min

Key Exclusion Criteria:

  1. Waldenström macroglobulinemia
  2. Multiple myeloma of Immunoglobin M (IgM) subtype
  3. POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  4. Plasma cell leukemia (> 2.0 × 109/L circulating plasma cells by standard differential)
  5. Myelodysplastic syndrome
  6. Second malignancy within the past 5 years except:

    • Adequately treated basal cell or squamous cell skin cancer
    • Carcinoma in situ of the cervix
    • Prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months
    • Ductal breast carcinoma in situ with full surgical resection (i.e., negative margins)
    • Treated medullary or papillary thyroid cancer
    • Similar condition with an expectation of > 95% five-year disease-free survival
  7. History of or current amyloidosis
  8. Cytotoxic chemotherapy within the 28 days prior to randomization
  9. Immunotherapy within the 21 days prior to randomization
  10. Glucocorticoid therapy within the 14 days prior to randomization that exceeds a cumulative dose of 160 mg of dexamethasone or 1000 mg prednisone
  11. Radiation therapy:

    • Focal therapy within the 7 days prior to randomization
    • Extended field therapy within the 21 days prior to randomization
  12. Prior treatment with either carfilzomib or oprozomib
  13. Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
  14. Contraindication to dexamethasone or any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to pre-existing pulmonary or cardiac impairment
  15. Active congestive heart failure (New York Heart Association [NYHA] Class III or IV, refer to Appendix F), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, acute diffuse infiltrative pulmonary disease, pericardial disease, or myocardial infarction within 6 months prior to enrollment
  16. Active infection within the 14 days prior to randomization requiring systemic antibiotics
  17. Pleural effusions requiring thoracentesis within the 14 days prior to randomization
  18. Ascites requiring paracentesis within the 14 days prior to randomization
  19. Ongoing graft-versus-host disease
  20. Uncontrolled hypertension or uncontrolled diabetes despite medication
  21. Significant neuropathy (≥ Grade 3) within the 14 days prior to randomization
  22. Known cirrhosis

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): NCT02412878


  Show 140 Study Locations
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02412878     History of Changes
Other Study ID Numbers: CFZ014
2014-005325-12 ( EudraCT Number )
First Posted: April 9, 2015    Key Record Dates
Last Update Posted: June 12, 2018
Last Verified: June 2018

Additional relevant MeSH terms:
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 acetate
Dexamethasone
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