Infusional Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01351623
Recruitment Status : Completed
First Posted : May 11, 2011
Results First Posted : March 13, 2017
Last Update Posted : April 13, 2017
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

May 9, 2011
May 11, 2011
January 3, 2017
March 13, 2017
April 13, 2017
May 9, 2011
January 26, 2016   (Final data collection date for primary outcome measure)
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
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.
Complete list of historical versions of study NCT01351623 on Archive Site
Not Provided
  • 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.
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Infusional Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma
Phase II Study of Infusional Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma

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.

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Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Multiple Myeloma
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.
Experimental: Carfilzomib
A single arm, open-label, single institution phase 2 clinical trial is planned.
Intervention: Drug: Carfilzomib
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 Identifier (NCT Number) in Medline.
Same as current
January 26, 2016
January 26, 2016   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States
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Memorial Sloan Kettering Cancer Center
Memorial Sloan Kettering Cancer Center
Principal Investigator: Nikoletta Lendvai, MD,PhD Memorial Sloan Kettering Cancer Center
Memorial Sloan Kettering Cancer Center
March 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP