The purpose of this study is to find out what effects new combinations of treatment will have
this disease. New promising treatment strategies will be added to this study as they are
available to be compared against the standard treatment.
This research is being done to try to find new combinations of treatment that may be better
for treating patients with this disease. It is not clear however if these treatments can
offer better results than standard treatment.
The study uses a "pick the winner" design to facilitate efficient screening of novel
combination treatment regimens and select those meeting pre-specified criteria for testing in
the phase III setting. All novel treatment options will be compared against the standard
treatment for this disease: rituximab plus gemcitabine, dexemthasone, and cisplatin (R-GDP).
- 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 most recent relapse (biopsy
proof of transformation is mandatory);
- Unclassifiable B-cell lymphoma with indeterminate features between diffuse large
B-cell lymphoma and Burkitt lymphoma.
- Biopsy proof of disease at initial diagnosis is mandatory. A repeat biopsy in primary
refractory disease is preferred but not mandatory to confirm progressive disease. A
biopsy at relapse is preferred but not mandatory. Participating centres must designate
a local reference expert pathologist who will confirm the diagnosis for the patients
enrolled at that centre.
- Patients must be CD20+ in order to be eligible for the study.
- Clinically and/or radiologically measurable disease (one site bidimensionally
measurable). Measurements/ evaluations must be done within 28 days prior to
- Prior FDG-PET scan, if done at baseline, must be positive (known FDG-avid lymphoma)
- Patients with de novo aggressive B-cell lymphoma must have relapsed or progressed, or
have refractory disease, after 1 prior line of therapy (R-CHOP chemotherapy or
equivalent). Patients with histological transformation from low grade lymphoma may
have had up to 3 prior treatment regimens. Patients with transformed low grade
lymphoma treated with a non-anthracycline regimen may be enrolled at investigator
- Patient age is ≥16 years. Patients older than 65 years of age are not recommended for
- ECOG performance status of 0, 1 or 2.
- Patient must be considered fit for intensive chemotherapy and ASCT, and an appropriate
candidate to receive second-line salvage chemotherapy and ASCT.
- Life expectancy > 90 days.
- Laboratory Requirements: (must be done within 14 days of randomization)
- Granulocytes (AGC) ≥ 1.0 x 10^9/L (independent of growth factor support)
- Platelets ≥ 100 x 10^9/L (50 x 10^9/L if bone marrow involvement by lymphoma,
independent of transfusion support)
- AST and ALT ≤ 3x ULN (if both are done, both must be <3x UNL)
- 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
Women must be post-menopausal, surgically sterile or use reliable forms of contraception
while on study. Women of child bearing potential and men who are sexually active must be
practicing a highly effective method of birth control during and after the study consistent
with local regulations regarding the use of birth control methods for subjects
participating in clinical trials. Men must agree to not donate sperm during and after the
study. These restrictions apply for 12 months (1 year) after the last dose of study drug.
- Women of childbearing potential must have a pregnancy test taken (either by serum
beta-human chorionic gonadotropin [B-hCG]) or urine) and proven negative within 14
days prior to randomization. Women who are pregnant or breastfeeding are ineligible
for this study.
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.
Patients must be accessible for treatment and follow up. Patients randomized on this trial
must be treated and followed at the participating centre. This implies there must be
reasonable geographical limits (for example: 1 ½ hour's driving distance) placed on
patients being considered for this trial. 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.
In accordance with CCTG policy, protocol treatment is to begin within 5 working days of
- 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 tumours curatively
treated with no evidence of disease for ≥ 3 years.
- 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.
- Major surgery performed within 10 days of randomization.
- 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 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 are eligible.
- Patients who have been vaccinated with live, attenuated vaccines within 4 weeks of
- 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.
- 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.
- 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, interfere with the absorption or metabolism of selinexor tablets, or
preclude safe administration of the planned protocol treatment or required follow-up,
including (for example):
- active, uncontrolled bacterial, fungal, or viral infection;
- clinically significant cardiac dysfunction or cardiovascular disease.
- Pregnant or lactating females, or women of childbearing potential not willing to use
an adequate method of birth control for the duration of the study.
- Patients are not eligible if they have a known hypersensitivity to the study drugs or