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

NCT ID: NCT01386398

Last Updated: 2015-01-21

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL

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.

Conditions

Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

bortezomib

Intervention Type: DRUG

vorinostat

Intervention Type: DRUG

laboratory biomarker analysis

Intervention Type: OTHER

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Principal Investigators

Pablo Luis Ortiz-Romero

Role:

Hospital Universitario 12 de Octubre

References

Valipour A, Jager M, Wu P, Schmitt J, Bunch C, Weberschock T. Interventions for mycosis fungoides. Cochrane Database Syst Rev. 2020 Jul 7;7(7):CD008946. doi: 10.1002/14651858.CD008946.pub3.

Reference Type: DERIVED

PMID: 32632956 (View on PubMed)

Other Identifiers

EORTC-21082

Identifier Type: -

Identifier Source: secondary_id

EU-21116

Identifier Type: -

Identifier Source: secondary_id

EUDRACT-2009-011021-13

Identifier Type: -

Identifier Source: secondary_id

EORTC-21082

Identifier Type: -

Identifier Source: org_study_id