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

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-012280-34-FR
• Date of registration: 08/01/2010
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International N.V.
• 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
• 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
• Date of first enrolment: 25/02/2010
• Target sample size: 164
• Recruitment status: Authorised-recruitment may be ongoing or finished
• 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:
Potential subjects must satisfy all of the following criteria to be enrolled in the study:
• 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
– 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 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
• 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
• Women must be:
– postmenopausal for at least 1 year (must not have had a natural menses for at least 12 months),
– surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal
ligation, or otherwise be incapable of pregnancy),
– abstinent (at the discretion of the investigator/per local regulations), or
– if sexually active, be practicing a highly effective method of birth control
(eg, prescription oral contraceptives, contraceptive injections, contraceptive patch,
intrauterine device, double-barrier method (eg, condoms, diaphragm, or cervical
cap, with spermicidal foam, cream, or gel, male partner sterilization) as local
regulations permit, before entry, and must agree to continue to use the same
method of contraception throughout the study. They must also be prepared to
continue birth control measures for at least 6 months after terminating treatment.
• Women of childbearing potential must have a negative serum or urine ß-human
chorionic gonadotropin (ß-hCG) pregnancy test at screening
• Men must agree to use an acceptable method of contraception (for themselves or
female partners as listed above) for the duration of the study. Men must agree to use a double barrier method of birth control and to not donate sperm during the study and for 3 months after receiving the last dose of study drug
• Willing/able to adhere to the prohibitions and restrictions specified in this protocol
• All subjects (or their legally-acceptable representatives) must have signed an
informed consent document indicating that they understand the purpose of and
procedures required for the study and are willing to participate in the study
• To participate in the optional pharmacogenomic component of this study, subjects (or their legally-acceptable representative) must have signed the informed consent form for pharmacogenomic research indicating willingness to participate in the
pharmacogenomic component of the study (where local regulations permit). Refusal
to give consent for this component does not exclude a subject from participation in
the clinical study. Acquisition of t
Exclusion criteria:
Potential subjects who meet any of the following criteria will be excluded from
participating in the study:
History of disallowed therapies:
• 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, 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 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: 12.0 Level: LLT Classification code 10012818 Term: Diffuse large B-cell lymphoma

Intervention(s)

Trade Name: VELCADE
Product Name: VELCADE
Product Code: JNJ-26866138
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: BORTEZOMIB
CAS Number: 179324-69-7
Current Sponsor code: JNJ-26866138
Other descriptive name: VELCADE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3.5-

Trade Name: ENDOXAN
Product Name: ENDOXAN
Product Code: L01AA01
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: CYCLOPHOSPHAMIDE
CAS Number: 50180
Other descriptive name: ENDOXAN
Concentration unit: g gram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Doxorubicin
Product Name: DOXORUBICIN
Product Code: L01DB01
Pharmaceutical Form: Solution for injection
INN or Proposed INN: DOXORUBICIN
CAS Number: 23214-92-8
Concentration unit: % (W/V) percent weight/volume
Concentration type: equal
Concentration number: 0.2-

Trade Name: Decortin
Product Name: Decortin
Product Code: H02AB07
Pharmaceutical Form: Tablet
INN or Proposed INN: PREDNISONE
CAS Number: 53-03-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: MabThera
Product Name: Mabthera
Pharmaceutical Form: Solution for injection
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: Vincrisin
Product Name: Vincrisin
Pharmaceutical Form: Solution for injection
INN or Proposed INN: VINCRISTINE SULFATE
CAS Number: 2068-78-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-

Trade Name: Decortin
Product Name: Decortin
Pharmaceutical Form: Tablet
INN or Proposed INN: PREDNISONE
CAS Number: 53-03-2
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-

Trade Name: MabThera
Product Name: Mabthera
Pharmaceutical Form: Solution for injection
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit:

Primary Outcome(s)

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 Objective: The secondary objectives are to determine overall response rate (CR + partial response);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 rates; determine Kaplan-Meier estimates of 1- and 2-year overall survival rates; determine the safety profile of the VR-CAP regimen; correlate immunohistochemistry & gene expression profiling or quantitative reverse transcription polymerase chain reaction data to identify the non-GCB subtype of DLBCL; identify RNA-based signatures that correlate with response to drug treatment; assess the change in fatigue and patient utility scores for the VR-CAP and R-CHOP treatment groups; explore the measurement properties of the EORTC QLQ-C30 and the EQ-5D in this patient population; collect medical resource utilization data that may be used in future economic modeling

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

Secondary ID(s)

26866138-LYM-2034

2009-012280-34-BE