Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma (ARROW)
Multiple Myeloma

About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Key Inclusion Criteria:
- Relapsed multiple myeloma
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
- At least 2 but no more than 3 prior therapies for multiple myeloma
- Prior exposure to an immunomodulatory agent (IMiD)
- Prior exposure to a proteasome inhibitor (PI)
- Documented response of at least partial response (PR) to 1 line of prior therapy
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
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- Left ventricular ejection fraction (LVEF) ≥ 40% within the 21 days prior to randomization
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:
- Waldenström macroglobulinemia
- Multiple myeloma of Immunoglobin M (IgM) subtype
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Plasma cell leukemia (> 2.0 × 10⁹/L circulating plasma cells by standard differential)
- Myelodysplastic syndrome
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
- History of or current amyloidosis
- Cytotoxic chemotherapy within the 28 days prior to randomization
- Immunotherapy within the 21 days prior to randomization
- Glucocorticoid therapy within the 14 days prior to randomization that exceeds a cumulative dose of 160 mg of dexamethasone or 1000 mg prednisone
Radiation therapy:
- Focal therapy within the 7 days prior to randomization
- Extended field therapy within the 21 days prior to randomization
- Prior treatment with either carfilzomib or oprozomib
- Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
- 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
- Active congestive heart failure (New York Heart Association [NYHA] Class III or IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, acute diffuse infiltrative pulmonary disease, pericardial disease, or myocardial infarction within 6 months prior to enrollment
- Active infection within the 14 days prior to randomization requiring systemic antibiotics
- Pleural effusions requiring thoracentesis within the 14 days prior to randomization
- Ascites requiring paracentesis within the 14 days prior to randomization
- Ongoing graft-versus-host disease
- Uncontrolled hypertension or uncontrolled diabetes despite medication
- Significant neuropathy (≥ Grade 3) within the 14 days prior to randomization
- Known cirrhosis
Sites / Locations
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- Mayo Clinic
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- Center for Cancer and Blood Disorders
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- Maryland Oncology Hematology, P.A
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- John Theurer Cancer Center at Hackensack University Medical Center
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- Blood and Cancer Center of East Texas
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Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Once-weekly Carfilzomib 20/70 mg/m² + Dexamethasone
Twice-weekly Carfilzomib 20/27 mg/m² + Dexamethasone
Participants received carfilzomib administered by intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle (20 mg/m² on day 1 of cycle 1 and 70 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
Participants received carfilzomib administered by IV infusion on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle (20 mg/m² on days 1 and 2 of cycle 1 and 27 mg/m² thereafter). Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.