Carfilzomib in Treating Patients With Relapsed or Refractory T-Cell Lymphoma

This study is currently recruiting participants.
Verified April 2014 by University of Nebraska
Sponsor:
Collaborators:
Onyx Pharmaceuticals
Information provided by (Responsible Party):
Julie M Vose, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT01336920
First received: March 23, 2011
Last updated: April 17, 2014
Last verified: April 2014
  Purpose

This phase I trial studies the side effects and best dose of carfilzomib in treating patients with relapsed or refractory T-cell lymphoma. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Adult Nasal Type Extranodal NK/T-cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Peripheral T-cell Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Drug: carfilzomib
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Carfilzomib for the Treatment of T-Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by University of Nebraska:

Primary Outcome Measures:
  • MTD of carfilzomib, determined by incidence of dose-limiting toxicity (DLT) as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Incidence of adverse events, assessed by the NCI CTCAE version 4.0 [ Time Frame: Up to 30 days after completion of study treatment ] [ Designated as safety issue: Yes ]
    The incidence rates of adverse events will be described by for each dose level. The frequency of occurrence of overall toxicity, categorized by toxicity grades, will be described.


Estimated Enrollment: 15
Study Start Date: June 2011
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (carfilzomib)
Patients receive carfilzomib IV over 30 minutes on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Drug: carfilzomib
Given IV
Other Names:
  • Kyprolis
  • PR-171
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To establish the maximum tolerated dose (MTD) of single agent carfilzomib in patients with relapsed and refractory peripheral T-cell lymphoma (PTCL) including angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL) anaplastic lymphoma receptor tyrosine kinase (ALK)+/ALK-, adult T-cell leukemia/lymphoma (ATLL), natural killer (NK)-cell lymphoma (NKL), transformed mycosis fungoides (MF) to large cell, and PTCL-unspecified (PTCL-U).

II. To assess the safety and preliminary efficacy of single agent carfilzomib in patients with relapsed and refractory peripheral T-cell lymphoma (PTCL) including angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL) ALK+/ALK-, adult T-cell leukemia/lymphoma (ATLL), NK-cell lymphoma (NKL), transformed mycosis fungoides (MF) to large cell, and PTCL-unspecified (PTCL-U).

III. To evaluate nuclear transcription factor kappa-B (NF-kappa B) activation in PTCL tumor tissue and correlate that with response to carfilzomib, a novel proteosome inhibitor, which targets NF-kappa B.

OUTLINE: This is a dose escalation study.

Patients receive carfilzomib intravenously (IV) over 30 minutes on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for year 1, then every 4 months for year 2, then every 6 months for years 3 and 4, and then yearly thereafter.

  Eligibility

Ages Eligible for Study:   19 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Relapsed and refractory peripheral T-cell lymphoma (PTCL), including angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma (ALCL) ALK+/ALK-, adult T-cell leukemia/lymphoma (ATLL), NK-cell lymphoma (NKL), transformed mycosis fungoides (MF) to large cell, and PTCL-unspecified (PTCL-U) patients who have failed standard therapy/transplant for their histological confirmed disease or who are not transplant eligible are eligible to participate in this trial
  • Expected survival duration of >= three months
  • Karnofsky performance status >= 70
  • Absolute neutrophil count (ANC) >= 700 cells/mm^3, unless due to lymphoma involvement of the bone marrow or spleen
  • Platelet count >= 50 mm^3, unless due to lymphoma involvement of the bone marrow or spleen
  • Hemoglobin >= 8 g/dL, unless due to lymphoma involvement of the bone marrow
  • Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 3 x upper limits of normal (ULN) unless due to lymphoma or due to Gilberts disease
  • Bilirubin =< 3 x ULN unless due to lymphoma or due to Gilberts disease
  • Serum creatinine < 2.0 mg/dL or calculated creatinine clearance (CrCl) > 40 mL/min
  • Left ventricle ejection fraction (LVEF) >= 40% 2-dimensional (D) transthoracic echocardiogram (ECHO) is the preferred method of evaluation; multigated acquisition scan (MUGA) is acceptable if ECHO is not available
  • Able to adhere to the study visit schedule and other protocol requirements
  • Patients must be willing to give written informed consent, and sign an institutionally approved consent form before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
  • Non-pregnant and non-nursing; men and women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while on the study
  • No serious disease or condition that, in the opinion of the investigator, would compromise the patient's ability to participate in the study
  • Patients with a history of coronary artery disease, congestive heart failure, hypertension, diabetes, or hyperlipidemia must have an estimated ejection fraction >= 0.45 (45%) by multi-gated acquisition scan (MUGA) or echocardiography, performed within two months of study entry

Exclusion Criteria:

  • Pregnant or breast feeding females
  • Active serious infection requiring treatment (IV antibiotic, antivirals, or antifungals) within 14 days prior to the start of carfilzomib
  • Active hepatitis or uncontrolled human immunodeficiency virus (HIV)
  • Unstable angina or myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker
  • Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to the start of carfilzomib
  • Patients in whom the schedule of oral and IV fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment, will not be eligible to participate in the clinical trial
  • Prior malignancies within the past 2 years with exception of adequately treated basal cell, squamous cell skin cancer, or thyroid cancer; carcinoma in situ of the cervix or breast; prostate cancer of Gleason grade 6 or less with stable prostate specific antigen (PSA) levels
  • Significant peripheral neuropathy (grades 3-4, or grade 2 with pain) within 14 days prior to the start of carfilzomib
  • Known history of allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
  • Concurrent use of other anti-cancer agents, investigative agents, or treatments
  • Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
  • Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01336920

Locations
United States, Georgia
Emory University/Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Mary Jo Lechowicz    404-778-1868    mlechow@emory.edu   
Principal Investigator: Mary Jo Lechowicz         
United States, Nebraska
University of Nebraska Medical Center Recruiting
Omaha, Nebraska, United States, 68198
Contact: Julie M. Vose    402-559-3848    jmvose@unmc.edu   
Principal Investigator: Julie M. Vose         
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Michelle A. Fanale    713-792-2860    mfanale@mdanderson.org   
Principal Investigator: Michelle A. Fanale         
Sponsors and Collaborators
University of Nebraska
Onyx Pharmaceuticals
Investigators
Principal Investigator: Julie Vose University of Nebraska
  More Information

No publications provided

Responsible Party: Julie M Vose, MD, Principal Investigator, University of Nebraska
ClinicalTrials.gov Identifier: NCT01336920     History of Changes
Other Study ID Numbers: 518-10, NCI-2010-02257, 518-10, P50CA136411, P30CA036727
Study First Received: March 23, 2011
Last Updated: April 17, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Extranodal NK-T-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid

ClinicalTrials.gov processed this record on April 23, 2014