Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma

As rituximab-based regimens have become standard first-line treatment in CD20 positive
DLBCL, the efficacy of rituximab combined with salvage chemotherapy in the second-line
setting has decreased and there is a need for new therapies in patients progressing or
relapsing after first-line rituximab-based therapy. Replacement of rituximab with ofatumumab
in the second-line setting, following progression/relapse after first-line
rituximab-containing regimens, offers the potential to overcome relative or complete
rituximab resistance and thus improve response rates, the ability to proceed to
consolidative HDT/ASCT, and overall survival.

Inclusion Criteria:

- Subjects with CD20 positive DLBCL or grade 3b follicular lymphoma (FL) at original
diagnosis.

- Refractory to, or relapsed following, first-line treatment with rituximab combined
with anthracycline- or anthracenedione-based chemotherapy as defined by the protocol.

- CT with involvement of 2 or more clearly demarcated lesions/ nodes with a long axis >
1.5 cm and short axis >= 1.0cm or 1 clearly demarcated lesion/ node with a long axis
> 2.0 cm and short axis >= 1.0 cm.

- Baseline FDG-PET scans must demonstrate positive lesions compatible with CT defined
anatomical tumor sites.

- Age 18 yrs or older.

- ECOG performance status of 0, 1 or 2.

- Eligible for high dose chemotherapy and ASCT.

- Resolution of toxicities from first-line therapy to a grade that in the opinion of
the investigator does not contraindicate study participation.

- Signed written informed consent.

Exclusion Criteria:

- Previous cancer therapy for lymphoma, with the exception of first-line rituximab/
anthracycline- or anthracenedione-based chemotherapy, monotherapy rituximab prior to
or combined with first-line chemotherapy, as maintenance therapy, and radiotherapy in
a limited field or as a part of the first-line treatment plan.

- Any anti-cancer therapy, except limited field radiotherapy, within 2 weeks prior to
start of study therapy.

- Planned post-randomization chronic glucocorticoid use (limited acute use is allowed
and defined by the protocol) unless administered as therapy for mild COPD or asthma.

- Clinically significant cardiac disease, active or chronic infections, serious
significant diseases, other cancer within last 5 years. History of significant
cerebrovascular disease.

- Prior treatment with anti-CD20 monoclonal antibodies with the exception of rituximab.

- Abnormal/ inadequate WBC count, liver, and kidney function.

- Pregnant or lactating women or female patients of child-bearing potential (or male
patients with such partners) not willing to use adequate contraception during and up
to 1 year following dosing completion.