Study Evaluating Chemotherapy in Combination With Inotuzumab Ozogamicin In Subjects With Non-Hodgkin's Lymphoma

• Drug: inotuzumab ozogamicin+rituximab +cyclophosphamide+vincristine+prednisone
  

  Day 1:

  Rituximab at 375 mg/m2 Cyclophosphamide at 375 mg/m2 (cohort 1), 550mg/m2 (cohort 2), 750 mg/m2 (cohort 3, 4) Vincristine at 1.4 mg/m2 (max 2 mg)

  Day 2 Inotuzumab ozogamicin at 0.8 mg/m2 (cohort 1, 2, 3), 1.3 mg/m2 (cohort 4)

  Days 1-5:

  Prednisone at 40 mg/m2

  Each cycle is 3 weeks, with a maximum of 6 cycles total.

  Other Name: CMC-544
• Drug: inotuzumab ozogamicin+rituximab+gemcitabine+cisplatinum+dexamethasone
  

  Day 1:

  Rituximab at 375 mg/m2 Gemcitabine at 500 mg/m2 (cohort 1, 2b, 3b), 1000mg/m2 (cohort 2a, 3a, 4, 5) Cisplatin at 37.5 mg/m2 (cohort 1, 2a), 50mg/m2 (cohort 2b, 3a), 75mg/m2 (cohort 3b, 4, 5)

  Day 2:

  Inotuzumab ozogamicin at 0.8 mg/m2 (cohort 1, 2a, 2b, 3a, 3b, 4), 1.3mg/m2 (cohort 5)

  Days 1-4:

  Dexamethasone at 40 mg

  Each cycle is 3 weeks, with a maximum of 6 cycles total.

  Other Name: CMC-544

• Experimental: Arm 1 (R-CVP)
  
  Subjects in arm 1 will be enrolled in dose escalation cohorts that will initially evaluate an escalating dose of cyclophosphamide in combination with set doses of inotuzumab ozogamicin, vincristine, prednisone, and rituximab.
  Intervention: Drug: inotuzumab ozogamicin+rituximab +cyclophosphamide+vincristine+prednisone
• Experimental: Arm 2 (R-GDP)
  
  Subjects in arm 2 will be enrolled in dose escalation cohorts that will initially evaluate escalating doses of gemcitabine and/or cisplatinum in combination with set doses of inotuzumab ozogamicin, dexamethasone, and rituximab.
  Intervention: Drug: inotuzumab ozogamicin+rituximab+gemcitabine+cisplatinum+dexamethasone

• Sangha R, Davies A, Dang NH, Ogura M, MacDonald DA, Ananthakrishnan R, Paccagnella ML, Vandendries E, Boni J, Goh YT. Phase 1 study of inotuzumab ozogamicin combined with R-GDP for the treatment of patients with relapsed/refractory CD22+ B-cell non-Hodgkin lymphoma. J Drug Assess. 2017 Aug 16;6(1):10-17. doi: 10.1080/21556660.2017.1315336. eCollection 2017.
• Ogura M, Tobinai K, Hatake K, Davies A, Crump M, Ananthakrishnan R, Ishibashi T, Paccagnella ML, Boni J, Vandendries E, MacDonald D. Phase I Study of Inotuzumab Ozogamicin Combined with R-CVP for Relapsed/Refractory CD22+ B-cell Non-Hodgkin Lymphoma. Clin Cancer Res. 2016 Oct 1;22(19):4807-4816. Epub 2016 May 6.

Inclusion Criteria:

• Dose escalation cohorts: subjects with diagnosis of CD22-positive Non-Hodgkin's Lymphoma (NHL) who have had at least 1 prior anticancer treatment, including prior treatment with rituximab and chemotherapy.
• Expanded maximum tolerated dose (MTD) confirmation and preliminary efficacy cohorts: subjects with diagnosis of CD22-positive NHL who have had at least 1 prior anticancer treatment, including prior treatment with rituximab and chemotherapy or newly diagnosed subjects who are not candidates for anthracycline-based therapy.
• At least 1 measurable disease lesion that is > 1 cm in the longest transverse diameter, with a product of the diameters > 2.25 cm2 by CT or magnetic resonance imaging (MRI).

Exclusion Criteria:

• Candidate for potentially curative therapy such as stem cell transplantation.
• Prior allogeneic hematopoietic stem cell transplantation (HSCT).
• Prior autologous transplantation, radioimmunotherapy, or other anti CD22 immunotherapy <= 6 months before the first dose of investigational product.
• More than 3 previous combination chemotherapy (2 or more cytotoxics) anticancer regimens.