Infusional Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Onyx Pharmaceuticals
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01351623
First received: May 9, 2011
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Carfilzomib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Infusional Carfilzomib in Patients With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To evaluate the best Overall Response Rate (ORR) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • To evaluate the safety [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Toxicity scoring will be done using NCI CTCAE v4.0.

  • time to progression (TTP) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 44
Study Start Date: May 2011
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Carfilzomib
A single arm, open-label, single institution phase 2 clinical trial is planned.
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01351623

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Onyx Pharmaceuticals
Investigators
Principal Investigator: Nikoletta Lendvai, MD,PhD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided by Memorial Sloan-Kettering Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01351623     History of Changes
Other Study ID Numbers: 10-228
Study First Received: May 9, 2011
Last Updated: February 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
PR-171 (CARFILZOMIB)
Chemotherapy
10-228

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases

ClinicalTrials.gov processed this record on October 20, 2014