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

Conditions: on-Germinal Center B-Cell Subtype of Diffuse Large B-Cell Lymphoma
MedDRA version: 13.1Level: PTClassification code 10012818Term: Diffuse large B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2009-012280-34-CZ

Lead Sponsor: Janssen-Cilag International N.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 164

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
• 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 clin

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