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)

Overview

About this study

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).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Craig Reeder, M.D.

Closed for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

More information

Publications

  • Twice a week carfilzomib at 27 mg/m is approved for treatment of relapsed or refractory multiple myeloma. Phase 1/2 CHAMPION-1, the first study exploring once-weekly carfilzomib dosing, established the maximum tolerated dose at 70 mg/m in combination with dexamethasone. We aimed to compare progression-free survival in patients with relapsed and refractory multiple myeloma given once weekly carfilzomib or twice weekly carfilzomib. Read More on PubMed

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

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CLS-20147461

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