A Randomized Phase IIb Placebo-Controlled Study of R-ICE Chemotherapy With and Without SGN-40 for Patients With DLBCL

• Adverse events, laboratory values, and anti-drug antibody immune responses. [ Time Frame: 9 weeks ] [ Designated as safety issue: Yes ]
• Partial response, failure free survival, overall survival, and response for one and two years following treatment. [ Time Frame: Every 3 months for 2 years ] [ Designated as safety issue: No ]

This is a randomized trial to estimate the activity of R-ICE plus SGN-40 vs. R-ICE plus placebo in patients with DLBCL. The study will assess safety and tolerability and will measure any additional clinical benefit observed in patients receiving SGN-40.

• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin

• Drug: SGN-40
  2-8 mg/kg IV. Cycle 1: Days -1, 3, 8, 15; Cycles 2, 3: Days 1, 8, 15.
  Other Name: dacetuzumab
• Drug: placebo
  Volume as equivalent to corresponding SGN 40 dose IV. Cycle 1: Days -1, 3, 8, 15. Cycles 2, 3: Days 1, 8, 15.
• Drug: rituximab
  375 mg/m2 IV. Cycle 1: Day -2; Cycles 2, 3: Day 1
  Other Name: Rituxan
• Drug: etoposide
  100 mg/m2 IV. Cycles 1-3: Days 1, 2 and 3.
  Other Name: Toposar, Vepesid
• Drug: carboplatin
  AUC=5 mg/mL min IV. Cycles 1-3: Day 2.
  Other Name: Paraplatin
• Drug: ifosfamide
  5 g/m2 24 hr. IV infusion. Cycles 1-3: Day2.
  Other Name: Ifex

• Experimental: 1
  SGN-40, rituximab, etoposide, carboplatin, ifosfamide
  Interventions:

  • Drug: SGN-40
  • Drug: rituximab
  • Drug: etoposide
  • Drug: carboplatin
  • Drug: ifosfamide
• Placebo Comparator: 2
  placebo, rituximab, etoposide, carboplatin, ifosfamide
  Interventions:

  • Drug: placebo
  • Drug: rituximab
  • Drug: etoposide
  • Drug: carboplatin
  • Drug: ifosfamide

Inclusion Criteria:

• Confirmed diagnosis of de novo or transformed DLBCL, or follicular grade 3b lymphoma.
• Received at least four cycles of first-line therapy with R-CHOP, or equivalent.
• Best clinical response to first-line therapy of stable disease, partial response, or complete response.
• At least one measureable lesion that is both greater than or equal to 1.5cm by radiographic imaging and by positive FDG-PET scan.

Exclusion Criteria:

• Leptomeningeal or central nervous system lymphoma.
• Received any therapy for relapsed or progressive disease except for local radiation, steroids, or rituximab.
• Received a hematopoietic stem cell transplant.