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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2011 by National Cancer Institute (NCI).
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01386398
First received: June 30, 2011
Last updated: July 6, 2011
Last verified: July 2011
  Purpose

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.


Condition Intervention Phase
Lymphoma
Drug: bortezomib
Drug: vorinostat
Other: laboratory biomarker analysis
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Vorinostat (Zolinza®) in Combination With (Velcade®) Versus Vorinostat Alone in Refractory or Recurrent Advanced CTCL: A Randomized Phase III Study.

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Response rate [ Designated as safety issue: No ]
  • Time to progression [ Designated as safety issue: No ]
  • Duration of response [ Designated as safety issue: No ]
  • Second cancers [ Designated as safety issue: No ]
  • Acute and late toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment: 189
Study Start Date: January 2012
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01386398

Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
Investigators
Investigator: Pablo Luis Ortiz-Romero Hospital Universitario 12 de Octubre
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT01386398     History of Changes
Other Study ID Numbers: CDR0000702425, EORTC-21082, EU-21116, EUDRACT-2009-011021-13
Study First Received: June 30, 2011
Last Updated: July 6, 2011
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage II mycosis fungoides/Sezary syndrome
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
stage II cutaneous T-cell non-Hodgkin lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
recurrent cutaneous T-cell non-Hodgkin lymphoma

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

ClinicalTrials.gov processed this record on July 20, 2014