Infusional Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma

Tracking Information
First Submitted Date ICMJE	May 9, 2011
First Posted Date ICMJE	May 11, 2011
Results First Submitted Date	January 3, 2017
Results First Posted Date	March 13, 2017
Last Update Posted Date	April 13, 2017
Study Start Date ICMJE	May 9, 2011
Actual Primary Completion Date	January 26, 2016 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: March 15, 2017)	To Evaluate the Best Overall Response Rate (ORR) [ Time Frame: 2 years ]; Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions
Original Primary Outcome Measures ICMJE; (submitted: May 10, 2011)	To Evaluate the Best Overall Response Rate (ORR) [ Time Frame: 2 years ]; Defined as stringent Complete Response (sCR), Complete Response (CR), Very Good Partial Response (VGPR), or Partial Response (PR) to four cycles of infusional carfilzomib with or without dexamethasone in patients with multiple myeloma (MM) meeting eligibility criteria.
Change History	Complete list of historical versions of study NCT01351623 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE; (submitted: May 10, 2011)	To evaluate the safety [ Time Frame: 2 years ]Toxicity scoring will be done using NCI CTCAE v4.0.; time to progression (TTP) [ Time Frame: 2 years ]Median TTP defined as the time from start of treatment to disease progression. Participants who do not have disease progression will be censored at their date of last response assessment or date of death.; duration of response (DOR) [ Time Frame: 2 years ]DOR is defined as the time from first evidence of PR or better [first observation of PR before confirmation] to disease progression, with deaths owing to causes other than progression censored.; progression free survival (PFS) [ Time Frame: 2 years ]Rate of PFS defined as the time from start of treatment to disease progression or death. PFS will be calculated for all patients who have received at least one dose of carfilzomib. Median duration of PFS will be reported.
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Infusional Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma
Official Title ICMJE	Phase II Study of Infusional Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma
Brief Summary	The purpose of this study is to test a new drug called carfilzomib. It is a type of drug called a proteasome inhibitor. Proteasome breaks down proteins that are no longer useful to the cell. When the proteasome is turned off by a drug (like carfilzomib), useless proteins cannot be broken down. Instead the proteins build up and cause the cell to die. Myeloma cells make a lot of protein and are especially in need of a functional proteasome to survive. Carfilzomib is not approved for use by the Food and Drug Administration to treat myeloma. It is considered an experimental drug. Previous studies have shown that carfilzomib is safe to use. This study will look at what the effects, good and/or bad, carfilzomib has on myeloma.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Multiple Myeloma
Intervention ICMJE	Drug: Carfilzomib; Following enrollment patients will be treated with single agent infusional carfilzomib at 56mg/m2. Carfilzomib will be administered intravenously over 30 minutes on Days 1, 2, 8, 9, 15 and 16 of a 28-day cycle. Dexamethasone 8 mg PO/IV will be administered prior to all carfilzomib doses during the first cycle.
Study Arms	Experimental: Carfilzomib; A single arm, open-label, single institution phase 2 clinical trial is planned.; Intervention: Drug: Carfilzomib
Publications *	Lendvai N, Hilden P, Devlin S, Landau H, Hassoun H, Lesokhin AM, Tsakos I, Redling K, Koehne G, Chung DJ, Schaffer WL, Giralt SA. A phase 2 single-center study of carfilzomib 56 mg/m2 with or without low-dose dexamethasone in relapsed multiple myeloma. Blood. 2014 Aug 7;124(6):899-906. doi: 10.1182/blood-2014-02-556308. Epub 2014 Jun 24.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: May 10, 2011)	44
Original Estimated Enrollment ICMJE	Same as current
Actual Study Completion Date	January 26, 2016
Actual Primary Completion Date	January 26, 2016 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Participants must meet all of the following inclusion criteria to be eligible to enroll in this study.; Patients meeting the criteria for symptomatic multiple myeloma that has relapsed or is refractory to at least 2 prior lines of therapy.; Previous therapy with bortezomib.; Previous therapy with thalidomide or lenalidomide.; Patients must have measurable disease and therefore must have at least one of the following: Serum M-protein ≥1 gm/dL (≥10 gm/L) Urine M-protein ≥200 mg/24 hr Serum FLC assay: involved FLC ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal.; Age ≥ 18 years; Eastern Cooperative Oncology Group (ECOG) performance status 0-2 Adequate hepatic function, with serum ALT ≤ 3.5 times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 14 days prior to enrollment; Absolute neutrophil count (ANC) ≥ 1.0 × 109/L within 14 days prior to enrollment Hemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to enrollment (participants may be receiving red blood cell [RBC] transfusions in accordance with institutional guidelines); Platelet count ≥ 50 × 109/L (≥ 30 × 109/L if thought to be secondary to myeloma involvement of the bone marrow ) within 14 days prior to enrollment (platelet transfusions are allowed); Creatinine clearance (CrCl) ≥ 15 mL/minute within 14 days prior to enrollment, either estimated or calculated using a standard formula (eg, Cockcroft and Gault); Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception.; Male participants must agree to practice contraception. Exclusion Criteria: Prior treatment with carfilzomib.; Known CNS involvement with myeloma; Pregnant or lactating females; Major surgery within 21 days prior to registration.; Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) within 7 days prior to enrollment; Known human immunodeficiency virus infection; Active hepatitis B or C infection; Unstable angina or myocardial infarction within 4 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless participant has a pacemaker; Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment.; Concurrent malignancies, except for treated non-melanoma skin cancer and cervical carcinoma in situ.; Significant neuropathy (Grades 3-4, ) within 14 days prior to enrollment; Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib); Contraindication to any of the required concomitant drugs or supportive treatments, including options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment; Concurrent therapy with any other anticancer therapeutic with activity against multiple myeloma; Concurrent therapy with investigative agents (e.g., antibiotics or antiemetics)
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01351623
Other Study ID Numbers ICMJE	10-228
Has Data Monitoring Committee	Not Provided
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Memorial Sloan Kettering Cancer Center
Study Sponsor ICMJE	Memorial Sloan Kettering Cancer Center
Collaborators ICMJE	Amgen
Investigators ICMJE	Principal Investigator: Nikoletta Lendvai, MD,PhD Memorial Sloan Kettering Cancer Center
PRS Account	Memorial Sloan Kettering Cancer Center
Verification Date	March 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP