| Eligibility |
Inclusion Criteria:
1. Patients with histologic diagnosis for one of the following histologies according to
the World Health Organization: documented at initial diagnosis or at relapse:
- Diffuse large cell lymphoma, B-cell (includes primary mediastinal B-cell
lymphoma, T-cell rich B-cell lymphoma);
- Previous indolent lymphoma (follicular lymphoma, marginal zone lymphoma,
including extranodal MALT lymphoma, lymphoplasmacytoid lymphoma) with
transformation to diffuse large B-cell lymphoma at relapse (biopsy proof of
transformation is mandatory);
- Follicular lymphoma grade 3B;
- Biopsy proof of disease at initial diagnosis is mandatory. A biopsy at relapse is
mandatory. A histological diagnosis (core or excisional biopsy) is strongly
encouraged; a cytological diagnosis is acceptable only in the event that tissue
cannot be obtained.
Patients must be CD20+ in order to be eligible for the study.
2. Clinically and/or radiologically measurable disease (1 site bidimensionally
measurable). Measurements/ evaluations must be done within 28 days prior to
registration.
Baseline FDG-PET scan, if available, must be positive (known FDG-avid lymphoma)
3. Patient must have had at least one previous regimen of therapy for their disease.
Patients must have relapsed or progressed after R-CHOP chemotherapy or equivalent.
4. Patient age is =16 years. Patients older than 70 years of age are not recommended for
this study. (Note that the lower age limit at each centre will be determined by that
centre's policy regarding the age at which an individual may sign his or her own
consent.)
5. ECOG performance status of 0, 1, 2 or 3.
6. Patient must be considered fit for intensive chemotherapy and ASCT and an appropriate
candidate to receive salvage chemotherapy and ASCT.
7. Laboratory Requirements: (must be done within 14 days of registration)
Hematology:
- Granulocytes (AGC) > 1.0 x 109/L (independent of growth factor support)
- Platelets > 100 x 109/L (50 x 109/L if bone marrow involvement by lymphoma,
independent of transfusion support)
Biochemistry:
- AST and ALT < 3x ULN
- Serum total bilirubin < 1.5x ULN (= 5x ULN if Gilberts Disease)
- Serum Creatinine < 1.5x ULN (or estimated GFR of =40 mL/min/1.73m2 using
Cockcroft Gault formula)
- International normalized ratio (INR) > 1.5 × the ULN in the absence of
therapeutic anticoagulation
- Partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT)
- > 1.5 × the ULN in the absence of a lupus anticoagulant
8. A Women of childbearing potential (WOCBP) is defined as any female who has experienced
menarche and who has not undergone surgical sterilization (hysterectomy or bilateral
oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of
amenorrhea in a woman over age 45 years in the absence of other biological or
physiological causes. Women of child bearing potential (who are heterosexually active)
and men (who are sexually active with WOCBP), must be practicing a highly effective
method of birth control (Pearl Index <1) such as oral contraceptives, intrauterine
device, sexual abstinence or barrier method of contraception in conjunction with
spermicidal jelly during study treatment and in female patients for 18 months after
end of antibody treatment Men must agree to not donate sperm during and after the
study. These restrictions apply for 18 months after the last dose of study drug.
Women of childbearing potential must have a pregnancy test taken (either by serum
beta-human chorionic gonadotropin [ß-hCG]) or urine) and proven negative within 14
days prior to registration.
Women who are pregnant or breastfeeding are ineligible for this study.
9. Patient consent must be appropriately obtained in accordance with applicable local and
regulatory requirements. Each patient must sign a consent form prior to enrollment in
the trial to document their willingness to participate.
10. Patients must be accessible for treatment and follow-up. Patients randomized on this
trial must be treated and followed at the participating centre. Investigators must
assure themselves the patients randomized on this trial will be available for complete
documentation of the treatment, response assessment, adverse events, and follow-up.
11. Protocol treatment is to begin within 5 working days of patient registration
Exclusion Criteria:
1. Patients who have been previously treated with obinutuzumab.
2. Life expectancy < 90 days
3. Patients with a history of other malignancies, except: adequately treated non-melanoma
skin cancer and superficial bladder cancer, curatively treated in-situ cancer of the
cervix or breast, or localized excised prostate cancer, other solid tumors curatively
treated with no evidence of disease for > 5 years.
4. Active and uncontrolled central nervous system involvement, meningeal or parenchymal.
Patients with CNS disease at initial presentation and who are in a CNS CR at the time
of relapse are eligible. MRI scanning and / or lumbar puncture should be performed if
there is clinical suspicion of active CNS disease.
5. Patients with symptoms suggestive of Progressive Multifocal Leukoencephalopathy (PML).
6. Major surgery performed within 4 weeks prior to registration.
7. Known history of human immunodeficiency virus (HIV), active Hepatitis C Virus
infection, active Hepatitis B Virus infection or any uncontrolled active systemic
infection requiring intravenous (IV) antibiotics. Patients with positive hepatitis B
serology are defined as positive Hepatitis B surface antigen (HBsAg) or core antibody
(anti-HBc). These patients should consult liver disease experts before start of
treatment and should be monitored and managed following local medical standards to
prevent hepatitis reactivation. Patients with Hepatitis B serology suggestive of
infection are eligible if they are HBV DNA negative and concurrently treated with
anti-viral therapy. Patients with a past history of hepatitis C who have eradicated
the virus (defined as negative PCR for HCV RNA) are eligible.
8. Patients who have been vaccinated with live, attenuated vaccines within 4 weeks prior
to registration.
9. Known history of stroke or intracranial hemorrhage within 6 months prior to
registration.
10. Clinically significant cardiovascular disease such as uncontrolled or symptomatic
arrhythmias, congestive heart failure, or myocardial infarction within 6 months of
Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by
the New York Heart Association Functional Classification.
11. Any serious active disease or co-morbid medical condition, including psychiatric
illness, judged by the local investigator to preclude safe administration of the
planned protocol treatment or required follow-up.
12. Any other serious intercurrent illness, life threatening condition, organ system
dysfunction, or medical condition judged by the local investigator to compromise the
subject's safety, preclude safe administration of the planned protocol treatment or
required follow-up, including (for example):
- Active, uncontrolled bacterial, fungal, or viral infection, history of chronic or
recurrent infection
- Clinically significant cardiac dysfunction or cardiovascular disease.
13. Patients are not eligible if they have a known hypersensitivity to the study drugs or
their component, or a history of severe allergic or anaphylactic reactions to
humanized or murine monoclonal antibodies, or a known sensitivity or allergy to murine
products
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