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

NCT01187446 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: IRB-18417SU-08092010-6685LYMNHL0078
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Cutaneous Lymphoma; Cutaneous T-cell Lymphoma

Keywords

Cutaneous T-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Clinical Response (CCR)

  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.

  Week 8

Secondary Outcomes (4)

• Safety and Tolerability as Measured by Severity and Frequency of Adverse Events

  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.

• Clinical Response Rate (CRR)

  Week 8

• Duration of Clinical Benefit (Per Protocol Follow-up)

  48 weeks after completion of treatment

• Duration of Clinical Benefit (Supplemental Follow-up)

  140 weeks

Study Arms (2)

TSEBT & Vorinostat

EXPERIMENTAL

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); Drug: Vorinostat

TSEBT only

ACTIVE COMPARATOR

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)

Interventions

Total skin electron beam therapy (TSEBT) RADIATION

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.

TSEBT & Vorinostat; TSEBT only

Vorinostat DRUG

Starting doses of is vorinostat 400 mg/day, continuing for 8 weeks.

Also known as: Zolinza

TSEBT & Vorinostat

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (3)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Zelenetz AD, Abramson JS, Advani RH, Andreadis CB, Byrd JC, Czuczman MS, Fayad L, Forero A, Glenn MJ, Gockerman JP, Gordon LI, Harris NL, Hoppe RT, Horwitz SM, Kaminski MS, Kim YH, Lacasce AS, Mughal TI, Nademanee A, Porcu P, Press O, Prosnitz L, Reddy N, Smith MR, Sokol L, Swinnen L, Vose JM, Wierda WG, Yahalom J, Yunus F. NCCN Clinical Practice Guidelines in Oncology: non-Hodgkin's lymphomas. J Natl Compr Canc Netw. 2010 Mar;8(3):288-334. doi: 10.6004/jnccn.2010.0021. No abstract available.

  PMID: 20202462 BACKGROUND

• Olsen E, Vonderheid E, Pimpinelli N, Willemze R, Kim Y, Knobler R, Zackheim H, Duvic M, Estrach T, Lamberg S, Wood G, Dummer R, Ranki A, Burg G, Heald P, Pittelkow M, Bernengo MG, Sterry W, Laroche L, Trautinger F, Whittaker S; ISCL/EORTC. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007 Sep 15;110(6):1713-22. doi: 10.1182/blood-2007-03-055749. Epub 2007 May 31.

  PMID: 17540844 BACKGROUND

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Results Point of Contact

• Title: Youn H Kim, MD
• Organization: Stanford University Medical Center

younkim@stanford.edu

650-521-3545

Study Officials

• Youn H Kim

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: August 20, 2010
• First Posted: August 24, 2010
• Study Start: December 1, 2010
• Primary Completion: August 1, 2013
• Study Completion: February 1, 2014
• Last Updated: November 20, 2017
• Results First Posted: November 20, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)