Clinical Trials /

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

NCT01336920

Description:

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.

Related Conditions:
  • Anaplastic Large Cell Lymphoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

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

Title

  • Brief Title: Carfilzomib in Treating Patients With Relapsed or Refractory T-Cell Lymphoma
  • Official Title: Phase I Study of Carfilzomib for the Treatment of T-Cell Lymphoma
  • Clinical Trial IDs

    NCT ID: NCT01336920

    ORG ID: 518-10

    NCI ID: NCI-2010-02257

    Trial Conditions

    Recurrent Adult T-cell Leukemia/Lymphoma

    Angioimmunoblastic T-cell Lymphoma

    Peripheral T-cell Lymphoma

    Anaplastic Large Cell Lymphoma

    Adult Nasal Type Extranodal NK/T-cell Lymphoma

    Trial Interventions

    Drug Synonyms Arms
    carfilzomib Kyprolis, PR-171 Treatment (carfilzomib)

    Trial 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.

    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.

    Trial Arms

    Name Type Description Interventions
    Treatment (carfilzomib) Experimental 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. carfilzomib

    Eligibility Criteria

    Inclusion Criteria:

    - Relapsed and refractory 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 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

    - Karnofsky performance status >= 70

    - 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

    - Liver functions (AST, ALT, bilirubin) =< 3 x upper limits of normal (ULN) unless due
    to lymphoma or due to Gilberts disease

    - Serum creatinine < 2.0 mg/dL or calculated creatinine clearance (CrCl) > 40 mL/min
    (Cockcroft-Gault)

    - LVEF >= 40% 2-D transthoracic ECHO is the preferred method of evaluation; MUGA scan
    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 a MUGA or echocardiography,
    performed within 2 months of study entry

    Exclusion Criteria:

    - Pregnant or breast feeding females

    - Active serious infection requiring treatment within 14 days prior to the start of
    carfilzomib

    - Active hepatitis or uncontrolled 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 EKG 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

    - 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

    Minimum Eligible Age: 19 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    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

    Secondary Outcome Measures

    Trial Keywords