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Low-dose (12 Gy) TSEBT+Vorinostat Versus Low-dose TSEBT Monotherapy in Mycosis Fungoides

This study has been terminated.
(Business decision by funding source)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01187446
First Posted: August 24, 2010
Last Update Posted: November 20, 2017
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.
Information provided by (Responsible Party):
Youn Kim, Stanford University
  Purpose

The purpose of this study is to determine if vorinostat combined with low-dose total skin electron beam therapy (TSEBT) offers superior clinical benefit (efficacy & safety) over low-dose TSEBT alone in participants with mycosis fungoides (MF)

Treatment in this study is TSEBT +/- vorinostat, with participants stratified by MF stage.


Condition Intervention Phase
Cutaneous Lymphoma Cutaneous T-cell Lymphoma Radiation: Total skin electron beam therapy (TSEBT) Drug: Vorinostat Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-label, Randomized, Phase I/II Study Evaluating the Safety and Efficacy of Low-dose (12 Gy) Total Skin Electron Beam Therapy (TSEBT) Combined With Vorinostat Versus Low-dose TSEBT Monotherapy in Mycosis Fungoides (MF)

Resource links provided by NLM:


Further study details as provided by Youn Kim, Stanford University:

Primary Outcome Measures:
  • Complete Clinical Response (CCR) [ Time Frame: Week 8 ]
    Complete Clinical Response (CCR) at week 8 as determined by an Modified Severity-Weighted Assessment Tool (mSWAT) score of 0. mSWAT is an objective, quantitative, severity-weighted method to assess the extent of mycosis fungoides (MF) lesions, and is determined by total body surface area (%TBSA) of the lesion by a severity-weighting factor (1 = patch; 2 = plaque; 4 = tumor). O% TBSA produces a product of 0, indicating complete response.


Secondary Outcome Measures:
  • Safety and Tolerability as Measured by Severity and Frequency of Adverse Events [ Time Frame: Adverse events were collected through 30 days after the last day of study therapy, or until the patient received an non-study treatment for lymphoma, whichever occurred first. ]
    Adverse events occurring at least 10% out of evaluable participants, and it's corresponding rate in the opposing arm.

  • Clinical Response Rate (CRR) [ Time Frame: Week 8 ]

    Clinical Response Rate (CRR) at week 8 as determined by an Modified Severity-Weighted Assessment Tool (mSWAT) score of 0, consisting of complete response (CR) rate; partial response (PR) rate; stable disease (SD) rate; or progressive disease (PD) rate.

    CR = 100% clearance of skin disease (mSWAT score = 0) PR = 50%to <100% clearance of skin disease as measured by > 50% decrease of mSWAT score compared with baseline SD = Not CR, PR, or PD

    PD = Whichever is met first of:

    1. > 25% increase in skin disease from baseline as measured by > 25% increase of mSWAT score compared with baseline
    2. New tumor (T3) lesions in patients without prior T3 lesions (T1, T2, T4) or
    3. In responders (confirmed), increase in skin disease over nadir by 50% of baseline as measured by mSWAT score of > [nadir + > 50% of baseline]
    4. Relapse applies to any new disease after confirmed CR

  • Duration of Clinical Benefit (Per Protocol Follow-up) [ Time Frame: 48 weeks after completion of treatment ]
    Duration of clinical benefit represents the period of time that clinical response was maintained. Duration of clinical benefit is reported as the median period of time from the initiation of treatment until progressive disease, as measured by the mSWAT skin assessment, and censored at the final per-protocol assessment (48 weeks)

  • Duration of Clinical Benefit (Supplemental Follow-up) [ Time Frame: 140 weeks ]
    Duration of clinical benefit represents the period of time that clinical response was maintained. Duration of clinical benefit is reported as the median period of time from the initiation of treatment or until progressive disease, as measured by the mSWAT skin assessment.


Enrollment: 28
Study Start Date: December 2010
Study Completion Date: February 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TSEBT & Vorinostat

Total skin electron beam therapy (TSEBT) will be performed per institution guidelines.

Vorinostat will be administered at a dose of 400 mg/day, starting one day prior to the initiation of TSEBT. During TSEBT, vorinostat should be taken in the morning and preferably prior to TSEBT.

Radiation: Total skin electron beam therapy (TSEBT)
TSEBT is administered as 12 Gy fractionated at 2 grey (Gy)/cycle (each cycle requiring 2 days of treatment); 4 days each week; for 3 weeks.
Drug: Vorinostat
Starting doses of is vorinostat 400 mg/day, continuing for 8 weeks.
Other Name: Zolinza
Active Comparator: TSEBT only
Total skin electron beam therapy (TSEBT) will be administered according to the Stanford 6-field technique or equivalent technique per institutional standards. Patients will receive a planned total skin dose of 12 grey (Gy) fractionated at 2 Gy/cycle (each cycle requiring 2 days of treatment); 4 days each week; for a total of 3 weeks. Supplements will routinely be applied to the perineum and soles as well as any other "shadowed" sites involved by disease, such as the inframammary regions (1-2 Gy fractions to a total dose of 12 Gy). Discrete tumors may receive additional "boost" treatment not to exceed 12 Gy.
Radiation: Total skin electron beam therapy (TSEBT)
TSEBT is administered as 12 Gy fractionated at 2 grey (Gy)/cycle (each cycle requiring 2 days of treatment); 4 days each week; for 3 weeks.

  Show Detailed Description

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA

  • Biopsy-confirmed mycosis fungoides (MF); clinical stage IB; IIA; IIB; or IIIB.
  • Patients must have failed or have been intolerant to at least one prior systemic or skin-directed therapy. This may include topical steroids if used as primary therapy for MF.
  • 18 years of age or older.
  • Eastern Cooperative Oncology Group (ECOG) of ≤ 2.
  • White blood cell (WBC) > 2000/uL
  • Platelet count > 75,000/mm3
  • Absolute neutrophil count (ANC) > 1000.
  • Bilirubin ≤ 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) ≤ 2.5 x UNL
  • Alanine aminotransferase (ALT) ≤ 2.5 x UNL
  • Alkaline phosphatase (liver fraction) ≤ 2.5 x ULN
  • Creatinine ≤ 1.5 x UNL OR creatinine clearance ≤ 60 mL/min for patients with creatinine levels > 1.5 x institutional ULN
  • Potassium level between 3.5 and 4.5
  • Magnesium level between 1.5 and 2.5
  • Required washout period for prior therapies

    • Topical therapy: 2 weeks
    • Systemic biologic, monoclonal antibody, or chemotherapy: 4 weeks
    • Phototherapy or radiotherapy (excluding TSEBT): 4 weeks
    • Other investigational therapy: 4 weeks
    • Note: patients with rapidly progressive disease may be treated earlier than required washout period; however, such circumstance must be discussed and approved by the protocol director at the primary site (Stanford).
  • Women of child-bearing potential (WOCBP) must have negative serum pregnancy test.
  • WOCBP must agree to use effective contraception, defined as oral contraceptives, intrauterine devices, double barrier method (condom plus spermicide or diaphragm) or abstain from sexual intercourse. WOCBP includes any female who has experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea for 12 consecutive months).
  • Male subjects must be willing to use an appropriate method of contraception (eg, condoms) or abstain from sexual intercourse and inform any sexual partners that they must also use a reliable method of contraception (eg, birth control pills) during the study.
  • Ability to understand and sign a written informed consent document.
  • Ability to comply with the treatment schedule

EXCLUSION CRITERIA

  • Prior courses of TSEBT (Note : localized skin-directed radiotherapy is allowed if administered at least 4 weeks prior to initiation on study).
  • Concomitant use of any anti-cancer therapy or immune modifier.
  • Receiving colony stimulating factors.
  • Prior allogeneic or autologous transplant.
  • Active infection or have received intravenous antibiotics, antiviral, or antifungal agents within 2 weeks prior to the start of the study drug.
  • Known history of human immunodeficiency virus (HIV), hepatitis B or C.
  • History of prior malignancy with the exception of cervical intraepithelial neoplasia, non-melanoma skin cancer, and adequately treated localized prostate carcinoma (PSA < 1.0). Patients with a history of other malignancies must have undergone potentially curative therapy and have no evidence of that disease for 5 years.
  • Uncontrolled intercurrent illness, condition, or circumstances that could limit compliance with the study, including, but not limited to the following: active infection, acute or chronic graft versus host disease, symptomatic congestive heart failure, unstable angina pectoris, medically significant cardiac arrhythmia, uncontrolled diabetes mellitus or hypertension, or psychiatric conditions.
  • Medically significant cardiac event in prior 6 months (ie, myocardial infarction, cardiac surgery.
  • Congenital long QT syndrome.
  • QTc interval > 480 msec on screening ECG.
  • Proven or suspected stage IV disease including patients with B2 (Sezary syndrome); N3 (frank LN disease); or M1 (visceral disease) categories; presence of reactive or dermatopathic lymphadenopathy (N1-2) or limited blood involvement (B1) is permitted.
  • Pregnant or lactating.
  • Unwilling to use reliable birth control methods.
  • Any other medical issue, including laboratory abnormalities, deemed by the Investigator to be likely to interfere with patient participation.
  • Unwilling or unable to provide informed consent.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01187446


Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, Connecticut
Yale University School of Medicine
New Haven, Connecticut, United States, 06520
United States, Texas
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Youn H Kim Stanford University
  More Information

Publications:
Responsible Party: Youn Kim, Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT01187446     History of Changes
Other Study ID Numbers: IRB-18417
SU-08092010-6685 ( Other Identifier: Stanford University )
LYMNHL0078 ( Other Identifier: OnCore )
First Submitted: August 20, 2010
First Posted: August 24, 2010
Results First Submitted: December 28, 2016
Results First Posted: November 20, 2017
Last Update Posted: November 20, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Youn Kim, Stanford University:
Cutaneous T-cell Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Mycoses
Mycosis Fungoides
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Vorinostat
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action