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