Phase 2
Completed N=116
A Study of Weekly Carfilzomib in Combination With Dexamethasone for Progressive Multiple Myeloma
Source: ClinicalTrials.gov NCT01677858 ↗Enrolled (actual)
116
Serious AEs
35.3%
Results posted
Aug 2017
Primary outcomePrimary: Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) — 0; 0; 1; 2 participants
Summary
The study had the following primary objectives:
* Phase 1: to determine the maximum tolerated dose (MTD) of once-weekly (QW) carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior therapies
* Phase 2: to estimate the overall response rate (ORR) for patients with relapsed or refractory multiple myeloma who received 1 to 3 prior therapies treated with carfilzomib and dexamethasone QW at the MTD established in phase 1.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs) |
0; 0; 1; 2 | — |
| PRIMARY Overall Response Rate (ORR) |
33.3; 100; 93.3; 66.7; 74.2; 76.9 | — |
| SECONDARY Clinical Benefit Response Rate |
66.7; 100.0; 100.0; 83.3; 80.9; 83.7 | — |
| SECONDARY Progression-free Survival |
13.6; NA; 21.0; 12.9; 15.3; 16.2 | — |
| SECONDARY Time To Progression |
13.6; NA; 21.0; 12.9; 16.2; 17.2 | — |
| SECONDARY Duration of Response |
18.9; NA; 16.3; 11.9; 18.0; 18.0 | — |
| SECONDARY Number of Participants With Adverse Events |
3; 3; 15; 6; 89; 1 | — |
| SECONDARY Time to Maximum Plasma Concentration of Carfilzomib |
0.25; 0.25; 0.25 | — |
| SECONDARY Maximum Plasma Concentration of Carfilzomib |
789; 2390; 3090 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Carfilzomib |
281; 1040; 1210 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) fo Carfilzomib |
259; 1040; 1160 | — |
| SECONDARY Area Under the Plasma Concentration-time Curve During the Dosing Interval (0-168 Hours) for Carfilzomib |
259; 1040; 1160 | — |
| SECONDARY Volume of Distribution Observed at Steady State (Vss) for Carfilzomib |
17.0; 14.2; 7.87 | — |
| SECONDARY Terminal Half-life (T1/2,z) for Carfilzomib |
0.648; 0.883; 0.816 | — |
| SECONDARY Clearance of Carfilzomib After IV Infusion |
147; 131; 138 | — |
| SECONDARY Mean Residence Time Observed From Time Zero to Infinity (MRT0-∞) for Carfilzomib |
0.118; 0.108; 0.0571 | — |
Eligibility Criteria
Inclusion Criteria
- Multiple myeloma with relapsing or progressive disease at study entry
- Measurable disease, as defined by 1 or more of the following (assessed within 21 days prior to enrollment):
- Serum M-protein ≥ 0.5 g/dL, or
- Urine M-protein ≥ 200 mg/24 hours, or
- Only in patients who do not meet a or b, then use serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal kappa/lambda ratio
- Prior treatment with 1 to 3 prior regimens for multiple myeloma for Phase 1 and Phase 2 (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy
- Age ≥ 18 years
- Life expectancy ≥ 6 months
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Adequate hepatic function within 21 days prior to enrollment, with bilirubin 50%) within 21 days prior to enrollment. Patients must not have received platelet transfusions for at least 7 days prior to obtaining the screening platelet count
- Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/min within 21 days prior to enrollment. Calculation based on standard formula, such as the Cockcroft and Gault: [(140 - Age) x Mass (kg) / (72 x Creatinine mg/dL)]; multiply result by 0.85 if female
- Written informed consent in accordance with federal, local, and institutional guidelines
- Female patients of childbearing 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 3 months following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations). Postmenopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from a pregnancy test
- Male patients must agree to use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with an FCBP
Exclusion Criteria
- Multiple myeloma of Immunoglobulin M (IgM) subtype
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
- Waldenström's macroglobulinemia
- Amyloidosis
- Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 7 days prior to enrollment
- Cytotoxic chemotherapy with approved or investigational anticancer therapeutics within 28 days prior to enrollment
- Treatment with bortezomib (Velcade®), thalidomide (Thalomid®) or lenalidomide (Revlimid®) within 21 days prior to enrollment
- Focal radiation therapy within 7 days prior to enrollment. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to enrollment (ie, prior radiation must have been to < 30% of the bone marrow)
- Immunotherapy within 21 days prior to enrollment
- Major surgery within 21 days prior to enrollment
- Active congestive heart failure (New York Heart Association [NYHA] Classes III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months prior to enrollment
- Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B virus [HBV]), or antifungal agents within 14 days prior to enrollment
- Known human immunodeficiency virus (HIV) seropositivity
- Known hepatitis B or C virus infection (except for patients with HBV who are receiving and responding to HBV antiviral therapy: these patients are allowed)
- Patients with known cirrhosis
- Second malignancy within the past 3 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
- Breast carcinoma in situ with full surgical r
Data sourced from ClinicalTrials.gov (NCT01677858). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.