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Vorinostat (Zolinza®) in Combination With (Velcade®) Versus Vorinostat Alone in Refractory or Recurrent Advanced CTCL: A Randomized Phase III Study.


Phase 3
18 Years
N/A
Not Enrolling
Both
Lymphoma

Thank you

Trial Information

Vorinostat (Zolinza®) in Combination With (Velcade®) Versus Vorinostat Alone in Refractory or Recurrent Advanced CTCL: A Randomized Phase III Study.


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.

Inclusion 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)

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival

Safety Issue:

No

Principal Investigator

Pablo Luis Ortiz-Romero

Investigator Affiliation:

Hospital Universitario 12 de Octubre

Authority:

Unspecified

Study ID:

CDR0000702425

NCT ID:

NCT01386398

Start Date:

January 2012

Completion Date:

Related Keywords:

  • Lymphoma
  • 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
  • Lymphoma
  • Lymphoma, T-Cell, Cutaneous

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