A Randomized, Open-Label, Multicenter, Phase 2 Study of the Combination of VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (VR CAP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects With Newly Diagnosed Non-Germinal Center B Cell Subtype of Diffuse Large B-Cell Lymphoma - ND

• Register: EUCTR
• Last refreshed on: 5 August 2013
• Main ID: EUCTR2009-012280-34-IT
• Date of registration: 19/03/2010
• Prospective Registration: No
• Primary sponsor: JANSSEN-CILAG INTERNATIONAL NV
• Public title: A Randomized, Open-Label, Multicenter, Phase 2 Study of the Combination of VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (VR CAP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects With Newly Diagnosed Non-Germinal Center B Cell Subtype of Diffuse Large B-Cell Lymphoma - ND
• Scientific title: A Randomized, Open-Label, Multicenter, Phase 2 Study of the Combination of VELCADE, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone (VR CAP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Subjects With Newly Diagnosed Non-Germinal Center B Cell Subtype of Diffuse Large B-Cell Lymphoma - ND
• Date of first enrolment: 15/03/2010
• Target sample size: 164
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012280-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Belgium, Czech Republic, France, Germany, Ireland, Italy, Portugal, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
Histologically confirmed non-GCB, de novo DLBCL The histological confirmation of non-GCB DLBCL must be done centrally. Paraffin-embedded tissue blocks must be sent to the central laboratory for confirmation of the non-GCB subtype by IHC prior to randomization (Attachment 1) CD20+ disease Stage II, III, or IV disease by the American Joint Committee on Cancer, NHL staging system. Stage 1 primary mediastinal (thymic) DLBCL is also eligible. At least 1 measurable site of disease (see Section 9.2.1.2, Definitions of Measurable and Assessable Disease) based on the Revised Response Criteria for Malignant Lymphoma (Cheson 2007) Man or women, aged 18 years or older (must be at least the legal age limit to be able to give informed consent within the jurisdiction the study is taking place.) Eastern Cooperative Oncology Group [ECOG] performance status of 0, 1, or 2 (Attachment 3) Absolute neutrophil count (ANC) ≥1,500 cells/μL Platelets ≥100,000 cells/μL. Subjects with thrombocytopenia due to bone marrow infiltration from DLBCL are eligible if platelets are ≥50,000 cells/μL. Alanine aminotransferase (ALT) ≤3 x upper limit of normal (ULN) Aspartate aminotransferase (AST) ≤3 x ULN Total bilirubin <2mg/dL, except in patients with Gilbert syndrome or in patients in whom the bilirubin rise is of non-hepatic origin Serum creatinine <1.5 x UNL or creatinine clearance ≥50 cc/min
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Prior treatment with VELCADE Transformed lymphomas (follicular, T-cell, or Hodgkin s lymphoma) Prior extended radiotherapy for lymphoma (extended field radiotherapy such as mantle field radiation and inverted Y field radiation) More than 150 mg/m2 of prior doxorubicin for any reason Major surgery within 3 weeks before randomization Prior chemotherapy for lymphoma Short course (maximum of 10 days; not exceeding 100 mg/day) prednisone or equivalent steroids are allowed to treat symptoms in subjects with advanced disease who entered the screening phase and are awaiting to be randomized. Peripheral neuropathy or neuralgia of Grade 2 or worse Active CNS lymphoma Pregnant or breast feeding Uncontrolled or severe cardiovascular disease, including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure (Attachment 4), uncontrolled angina, pericardial disease, cardiac amyloidosis, or left ventricular ejection fraction (LVEF) <45% Diagnosed or treated for a malignancy other than NHL except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, ductal carcinoma in situ of the breast, or other solid tumors curatively treated with no evidence of disease for >5 years Active systemic infection requiring treatment including active hepatitis B infection (carriers of hepatitis B are permitted to enter the study) Documented or suspected human immunodeficiency virus (HIV)/AIDS Known allergies, hypersensitivity, or intolerance to VELCADE, cyclophosphamide, rituximab, prednisone, doxorubicin, vincristine, or its excipients (refer to Section 14.1, Physical Description of Study Drug(s) or compounds containing boron, mannitol, or similar agents Serious medical condition, such as active peptic ulcer disease, acute diffuse interstitial pulmonary disease, uncontrolled diabetes, or psychiatric illness, likely to interfere with participation in this clinical study Concurrent treatment with another investigational agent. Concurrent participation in non-treatment studies is not excluded. Any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Non-Germinal Center B-Cell Subtype of diffuse Large B-Cell Lymphoma
MedDRA version: 12.1 Level: LLT Classification code 10012818 Term: Diffuse large B-cell lymphoma

Intervention(s)

Trade Name: VELCADE
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Bortezomib
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3.5-

Pharmaceutical Form: Tablet
INN or Proposed INN: Prednisone
Concentration type: equal

Pharmaceutical Form: Solution for injection
INN or Proposed INN: Rituximab
Concentration unit: mg/l milligram(s)/litre
Concentration type: equal
Concentration number: 10-

Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: Cyclophosphamide
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-

Pharmaceutical Form: Solution for injection
INN or Proposed INN: Doxorubicin
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-

Pharmaceutical Form: Solution for injection
INN or Proposed INN: Vincristine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Primary Outcome(s)

Secondary Objective: The secondary objectives are to: Determine overall response rate (ORR) (CR + partial response [PR]) Determine duration of response (CR or PR) Determine duration of CR Determine time to subsequent anti-lymphoma therapy Determine Kaplan-Meier estimates of 1- and 2-year progression-free survival (PFS) rates Determine Kaplan-Meier estimates of 1- and 2-year overall survival rates Determine the safety profile of the VR-CAP regimen Correlate immunohistochemistry (IHC) and gene expression profiling (GEP) or quantitative reverse transcription polymerase chain reaction (qRT-PCR) data to identify the non-GCB subtype of DLBCL Identify RNA-based signatures that correlate with response to drug treatment

Primary end point(s): The primary endpoint is CR which is defined as complete disappearance of all detectable clinical evidence of disease and desease-related symptoms present before therapy in subject with histologically-confirmed non GCB DLBCL

Main Objective: The primary objective is to determine the complete response (CR) rate following treatment with VR-CAP (VELCADE, rituximab, cyclophosphamide, doxorubicin, and prednisone) or standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy in subjects with newly diagnosed non-germinal center B-like (non-GCB) diffuse large B-cell lymphoma (DLBCL).

Secondary ID(s)

26866138-LYM-2034

2009-012280-34-BE