A Study Of Inotuzumab Ozogamicin Versus Investigator's Choice Of Chemotherapy In Patients With Relapsed Or Refractory Acute Lymphoblastic Leukemia

• Drug: inotuzumab ozogamicin
  
  Dose: inotuzumab ozogamicin 0.8-0.5 mg/m^2 IV, weekly, 3 times per cycle Cycle length: 21-28 days Total number of cycles: 6
• Drug: FLAG (fludarabine, cytarabine and G-CSF)
  
  Dose: cytarabine 2.0 g/m^2/day IV days 1-6 fludarabine30 mg/m^2/day IV days 2-6 Cycle length: 28 days Total number of cycles: 4
• Drug: HIDAC (high dose cytarabine)
  
  cytarabine 3 g/m^2 IV every 12 hours for up to 12 times
• Drug: cytarabine and mitoxantrone
  
  mitoxantrone 12 mg/m^2 IV days 1-3 cytarabine 200 mg/m^2/day IV over 7 days cycle length: 15-20 days Total number of cycles: 4

• Experimental: Arm A
  
  Intervention: Drug: inotuzumab ozogamicin
• Active Comparator: Arm B
  
  Interventions:
  

  • Drug: FLAG (fludarabine, cytarabine and G-CSF)
  • Drug: HIDAC (high dose cytarabine)
  • Drug: cytarabine and mitoxantrone

• Jabbour E, Gökbuget N, Advani A, Stelljes M, Stock W, Liedtke M, Martinelli G, O'Brien S, Wang T, Laird AD, Vandendries E, Neuhof A, Nguyen K, Dakappagari N, DeAngelo DJ, Kantarjian H. Impact of minimal residual disease status in patients with relapsed/refractory acute lymphoblastic leukemia treated with inotuzumab ozogamicin in the phase III INO-VATE trial. Leuk Res. 2020 Jan;88:106283. doi: 10.1016/j.leukres.2019.106283. Epub 2019 Nov 25.
• Fujishima N, Uchida T, Onishi Y, Jung CW, Goh YT, Ando K, Wang MC, Ono C, Matsumizu M, Paccagnella ML, Sleight B, Vandendries E, Fujii Y, Hino M. Inotuzumab ozogamicin versus standard of care in Asian patients with relapsed/refractory acute lymphoblastic leukemia. Int J Hematol. 2019 Dec;110(6):709-722. doi: 10.1007/s12185-019-02749-0. Epub 2019 Nov 13.
• Kantarjian HM, DeAngelo DJ, Stelljes M, Liedtke M, Stock W, Gökbuget N, O'Brien SM, Jabbour E, Wang T, Liang White J, Sleight B, Vandendries E, Advani AS. Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: Final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Cancer. 2019 Jul 15;125(14):2474-2487. doi: 10.1002/cncr.32116. Epub 2019 Mar 28.
• Jabbour EJ, DeAngelo DJ, Stelljes M, Stock W, Liedtke M, Gökbuget N, O'Brien S, Wang T, Paccagnella ML, Sleight B, Vandendries E, Advani AS, Kantarjian HM. Efficacy and safety analysis by age cohort of inotuzumab ozogamicin in patients with relapsed or refractory acute lymphoblastic leukemia enrolled in INO-VATE. Cancer. 2018 Apr 15;124(8):1722-1732. doi: 10.1002/cncr.31249. Epub 2018 Jan 30.
• Kebriaei P, Cutler C, de Lima M, Giralt S, Lee SJ, Marks D, Merchant A, Stock W, van Besien K, Stelljes M. Management of important adverse events associated with inotuzumab ozogamicin: expert panel review. Bone Marrow Transplant. 2018 Apr;53(4):449-456. doi: 10.1038/s41409-017-0019-y. Epub 2018 Jan 12.
• Kantarjian HM, DeAngelo DJ, Advani AS, Stelljes M, Kebriaei P, Cassaday RD, Merchant AA, Fujishima N, Uchida T, Calbacho M, Ejduk AA, O'Brien SM, Jabbour EJ, Zhang H, Sleight BJ, Vandendries ER, Marks DI. Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. Lancet Haematol. 2017 Aug;4(8):e387-e398. doi: 10.1016/S2352-3026(17)30103-5. Epub 2017 Jul 4.
• Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, Gökbuget N, O'Brien S, Wang K, Wang T, Paccagnella ML, Sleight B, Vandendries E, Advani AS. Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia. N Engl J Med. 2016 Aug 25;375(8):740-53. doi: 10.1056/NEJMoa1509277. Epub 2016 Jun 12.

Inclusion Criteria:

• CD22 expression
• Adequate liver and renal functions

Exclusion Criteria:

• Isolated extramedullary disease
• Active Central Nervous System [CNS] disease