Study of ACTR707 in Combination With Rituximab in Subjects With Relapsed or Refractory B Cell Lymphoma

Inclusion Criteria:

- signed written informed consent obtained prior to study procedures

- histologically-confirmed relapsed or refractory CD20+ B-cell lymphoma of one of the
following types, with documented disease progression or recurrence following the
immediate prior therapy: DLBCL (regardless of cell of origin or underlying molecular
genetics), MCL, PMBCL, Gr3b-FL, TH-FL (prior dx of FL before transforming to DLBCL).

- biopsy-confirmed CD20+ expression of the underlying malignancy with disease
progression following immediate prior therapy

- at least 1 measurable lesion on imaging.

- must have received adequate prior therapy for the underlying CD20+ B-cell lymphoma,
defined as an anti-CD20 mAb in combination with an anthracycline-containing
chemotherapy regimen (i.e. chemo-immunotherapy) and at least one of the following:

- biopsy-proven refractory disease after frontline chemo-immunotherapy

- relapse within 1 year from frontline chemo-immunotherapy and ineligible for
autologous hematopoietic stem cell transplant (auto-HSCT)

- for subjects with DLBCL, PMBCL, and Gr3b-FL: relapsed or refractory disease
following at least 2 prior regimens or following an auto-HSCT

- for subjects with TH-FL: relapsed or refractory disease following at least 2
prior regimens or following an auto-HSCT. At least 1 prior regimen with an
anti-CD20 mAb in combination with chemotherapy is required following documented
transformation

- for subjects with MCL (confirmed with cyclin D1 expression or evidence of
t(11;14) by cytogenetics, fluorescent in situ hybridization (FISH) or polymerase
chain reaction (PCR): relapsed or refractory disease after at least 1 prior
regimen with chemo-immunotherapy (prior auto-HSCT is allowable)

- ECOG 0 or 1

- life expectancy of at least 6 months

- platelet count greater than 50,000/µL

Exclusion Criteria:

- known active central nervous system (CNS) involvement by malignancy.

- prior treatment as follows:

- alemtuzumab within 6 months of enrollment

- fludarabine, cladribine, or clofarabine within 3 months of enrollment

- external beam radiation within 2 weeks of enrollment

- mAb (including rituximab) within 2 weeks of enrollment

- other lymphotoxic chemotherapy (including steroids except as below) within 2
weeks of enrollment

- experimental agents within 3 half-lives prior to enrollment, unless progression
is documented on therapy

- clinically significant cardiac disease

- clinically significant active infection

- clinically significant CNS disorder

- clinical history, prior diagnosis, or overt evidence of autoimmune disease

- known bone marrow involvement due to underlying malignant disease, in dose-escalation
phase only