Study Comparing Inotuzumab Ozogamicin In Combination With Rituximab Versus Defined Investigator's Choice In Follicular Non-Hodgkin's Lymphoma (NHL)

• Drug: inotuzumab ozogamicin
  IV administration, 1.8mg/m² on day 2 of each cycle every 28 days, for up to 8 cycles.
• Drug: rituximab
  IV administration, 375 mg/m² on day 1 of each cycle every 28 days, for up to 8 cycles.
• Drug: rituximab
  intravenous rituximab at a dose of 375 mg/m2 on day 1
• Drug: cyclophosphamide
  intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1
• Drug: vincristine
  intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1
• Drug: prednisone/prednisolone
  oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5
• Drug: mitoxantrone
  mitoxantrone 10 mg/m2 intravenous on day 2
• Drug: fludarabine
  fludarabine 25 mg/m2 intravenous on days 2 through 4
• Drug: dexamethasone
  oral dexamethasone 20 mg/day on days 1-5

• Experimental: A
  Subjects will receive rituximab intravenously at a dose level of 375 mg/m² on day 1 of each cycle followed by inotuzumab ozogamicin administered intravenously at a dose level of 1.8 mg/m2 on day 2. The sequence will be repeated every 28 days.
  Interventions:

  • Drug: inotuzumab ozogamicin
  • Drug: rituximab
• Active Comparator: B
  Subjects will receive the investigator's choice from the following rituximab-containing regimens: R-CVP or R-FND. The investigator's choice of therapy will be administered every 21 days. Dosing for R-CVP will be intravenous rituximab at a dose of 375 mg/m2 on day 1, intravenous cyclophosphamide at a dose of 750 mg/m2 on day 1, intravenous vincristine at a dose of 1.4 mg/m2 (not to exceed 2 mg) on day 1, and oral prednisone/prednisolone at a dose of 40 mg/m2 on days 1 through 5. Dosing for R-FND will be as follows: rituximab 375 mg/m2 intravenous on day 1, mitoxantrone 10 mg/m2 intravenous on day 2, fludarabine 25 mg/m2 intravenous on days 2 through 4 and oral dexamethasone 20 mg/day on days 1-5.
  Interventions:

  • Drug: rituximab
  • Drug: cyclophosphamide
  • Drug: vincristine
  • Drug: prednisone/prednisolone
  • Drug: mitoxantrone
  • Drug: fludarabine
  • Drug: dexamethasone

Inclusion Criteria:

• Subjects with a diagnosis of CD20 and CD22-positive, follicular lymphoma, who have received 1 or 2 prior regimens, at least 1 of which should have contained administration of rituximab (either as a single agent or in combination).
• Age 18 years or older.
• ECOG performance status <= 2.
• ANC >= 1.5 x 10^9/L (1500/mL) and platelets >= 75 x 10^9/L (75,000/mL), serum creatinine <= 1.5 x ULN and urine protein to creatinine ratio of <= 0.5, total bilirubin <= 1.5 x ULN, AST and ALT <= 2.5 x ULN.
• At least 1 measurable disease lesion that is >= 1.5 cm x 1.5 cm by CT or MRI, in an area of no prior radiation therapy, or documented progression in an area that was previously irradiated.

Exclusion Criteria:

• Subjects with clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3b follicular lymphoma.
• Subjects whose disease is rituximab refractory, meaning that they did not have a CR or PR, or that they experienced disease progression within 6 months from the initiation of the rituximab or rituximab containing treatment regimen administered immediately preceding study enrollment.