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Vorinostat With or Without Bortezomib in Treating Patients With Refractory or Recurrent Stage IIB, Stage III, or Stage IV Cutaneous T-Cell Lymphoma

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ClinicalTrials.gov Identifier: NCT01386398
Recruitment Status : Withdrawn (Company withdrew interest)
First Posted : July 1, 2011
Last Update Posted : January 21, 2015
Sponsor:
Information provided by:
European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information
First Submitted Date  ICMJE June 30, 2011
First Posted Date  ICMJE July 1, 2011
Last Update Posted Date January 21, 2015
Study Start Date  ICMJE Not Provided
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: June 30, 2011)
Progression-free survival
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 30, 2011)
  • Overall survival
  • Response rate
  • Time to progression
  • Duration of response
  • Second cancers
  • Acute and late toxicity
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vorinostat With or Without Bortezomib in Treating Patients With Refractory or Recurrent Stage IIB, Stage III, or Stage IV Cutaneous T-Cell Lymphoma
Official Title  ICMJE Progression Free Survival (PFS) Comparison Between Suberoylanilide Hydroxamic Acid (SAHA, Vorinostat TM) in Combination With Bortezomib (Velcade TM) and SAHA Alone in Refractory or Recurrent Advanced CTCL. A Randomized Study.
Brief Summary

RATIONALE: Vorinostat and bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether vorinostat is more effective when given alone or when given together with bortezomib in treating patients with refractory or recurrent cutaneous T-cell lymphoma.

PURPOSE: This randomized phase III trial is studying how well vorinostat works when given alone compared with vorinostat given together with bortezomib in treating patients with refractory or recurrent stage IIB, stage III, or stage IV cutaneous T-cell lymphoma.

Detailed Description

OBJECTIVES:

Primary

  • To determine if the combination of bortezomib plus vorinostat (SAHA) is more effective than vorinostat alone, in terms of prolonging progression-free survival, in patients with stage IIB-IV cutaneous T-cell lymphoma who have failed prior therapy.

Secondary

  • To determine the overall survival of these patients.
  • To determine the response rate in these patients.
  • To determine the time to progression in these patients.
  • To determine the duration of response in these patients.
  • To determine the incidence of second cancers in these patients.
  • To determine the acute and late toxicity of this regimen in these patients.
  • To determine if translational research may provide insight into disease mechanism and identify biomarkers useful for prediction of treatment response. (Exploratory)

OUTLINE: This is a multicenter study. Patients are stratified according to type of cutaneous T-cell lymphoma (mycosis fungoides vs erythrodermic mycosis fungoides/Sézary syndrome), number of prior chemotherapy regimens (1 vs ≥ 2), and country. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral vorinostat (SAHA) once daily in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients receive bortezomib IV on days 1, 4, 8, and 11 and oral vorinostat once daily on days 1-14. Treatment repeats every 21 days until progression or unacceptable toxicity.

Blood and tissue samples are collected periodically for translational research to provide insight into disease mechanism and identify biomarkers useful for prediction of treatment response.

After completion of study treatment, patients are followed up at 4 weeks and then every 3 months until disease progression.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE
  • Drug: bortezomib
  • Drug: vorinostat
  • Other: laboratory biomarker analysis
Study Arms  ICMJE Not Provided
Publications * Valipour A, Jäger M, Wu P, Schmitt J, Bunch C, Weberschock T. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2020 Jul 7;7:CD008946. doi: 10.1002/14651858.CD008946.pub3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: January 20, 2015)
0
Original Estimated Enrollment  ICMJE
 (submitted: June 30, 2011)
189
Study Completion Date  ICMJE Not Provided
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically confirmed advanced cutaneous T-cell lymphoma (CTCL), including its variants mycosis fungoides and Sézary syndrome

    • Stage IIB-IV disease
  • Relapsed or refractory disease, including any of the following:

    • Patients with clinical progression following EORTC-21081 protocol treatment
    • Intolerant to ≥ 1 prior intravenous chemotherapy, including denileukin diftitox, antibodies or antibody conjugates, or any other systemic therapy
  • No CNS involvement

PATIENT CHARACTERISTICS:

  • WHO performance status 0-2
  • Absolute neutrophil count > 1.5 x 10^9/L*
  • Platelet count > 100 x 10^9/L*
  • Hemoglobin > 9 g/dL*
  • WBC > 3 x 10^9/L*
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)*
  • AST and ALT ≤ 3 times ULN (in case of liver infiltration ≤ 5 x ULN)*
  • Serum creatinine ≤ 2.0 mg/dL*
  • Calculated creatinine clearance ≥ 60 mL/min
  • Electrolytes (including potassium and magnesium) ≤ 1 times ULN*
  • Not pregnant or nursing prior to the first dose of study treatment and until 4 weeks after the last study treatment
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study therapy
  • Able to swallow capsules and is able to take or tolerate oral medication on a continuous basis
  • No New York Heart Association class III-IV disease
  • None of the following known conditions:

    • Infectious disease
    • Autoimmune disease
    • Immunodeficiency
  • No known or active HIV and/or hepatitis A, B, or C infection
  • No NCI CTC grade 1 peripheral sensory neuropathy with pain or peripheral sensory or motor neuropathy ≥ grade II
  • No other malignancy within the past 5 years
  • No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule NOTE: *Patients with a buffer range from the normal values of +/- 5% for hematology and +/- 10% for biochemistry are acceptable, except for renal function.

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • Must have completely recovered from previous treatment toxicity
  • No prior splenectomy or splenic irradiation
  • No prior bortezomib and/or histone deacetylase inhibitors (including vorinostat [SAHA])
  • More than 4 weeks since prior chemotherapy, immunotherapy, radiotherapy, or surgery

    • In case of clear progression during previous treatment, 2 weeks of wash-out is enough
  • No concurrent chemotherapy, immunotherapy, radiotherapy, or surgery (except biopsies)
  • No concurrent steroid (prednisone or equivalent) dose > 20 mg/day

    • Prednisone ≤ 20 mg/day for treatment of disorders other than CTCL allowed
  • No concomitant use of other histone deacetylase inhibitors (e.g., valproic acid)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01386398
Other Study ID Numbers  ICMJE EORTC-21082
EORTC-21082
EU-21116
EUDRACT-2009-011021-13
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE European Organisation for Research and Treatment of Cancer - EORTC
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Investigator: Pablo Luis Ortiz-Romero Hospital Universitario 12 de Octubre
PRS Account European Organisation for Research and Treatment of Cancer - EORTC
Verification Date January 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP