A Phase 2, Multicenter, Randomized, Open-label Study of MEDI-551 in Adults With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Condition: Diffuse Large B-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: MEDI-551 2 mg/kg; Rituximab; ICE; DHAP; Autologous Stem Cell Transplant (ASCT); MEDI-551 4 mg/kg
Intervention description: MEDI-551 at the assigned dose will be administered via Intravenous (IV) infusion. Subjects will receive 3 cycles of M-ICE or M-DHAP unless CR is achieved at the end of Cycle 2, disease progression is noted at the end of Cycle 2, or a significant/serious drug related toxicity occurs (as per the opinion of the investigator).; Rituximab at 375 mg/m2 will be administered via IV infusion 2 days before the start of Cycle 1 and on Day 1 of each cycle. The infusion time for rituximab will be 50 400 mg/hr, depending on subject's tolerance. Subjects will receive 3 cycles of Rituximab with Ice (R ICE) or Rituximab with DHAP (R-DHAP) unless CR is achieved at the end of Cycle 2, disease progression is noted at the end of Cycle 2, or a significant/serious drug related toxicity occurs (as per the opinion of the investigator).; ICE will be administered via IV infusion as follows: ifosfamide 5 g/m2 continuously for 24 hours with mesna on Days 2 and 3; carboplatin AUC=5 mg/mL x min [800 mg maximum) on Day 2; etoposide 100 mg/m2 on Days 1, 2, and 3) in 21-day cycles.; DHAP will be administered via IV infusion as follows: dexamethasone 40 mg on Days 1, 2, 3, and 4; cisplatin 100 mg/m2 continuously for 24 hours on Day 1 of dosing cycle; cytarabine 2 g/m2 in 3-hour infusion repeated after 12 hours (2 doses) on Day 2 in 21-day cycles.; Subjects who achieve CR or PR will undergo stem cell harvest and autologous stem cell transplantation (ASCT) following standard institutional protocols.; MEDI-551 at the assigned dose will be administered via Intravenous (IV) infusion. Subjects will receive 3 cycles of M-ICE or M-DHAP unless CR is achieved at the end of Cycle 2, disease progression is noted at the end of Cycle 2, or a significant/serious drug related toxicity occurs (as per the opinion of the investigator).
Intervention MeSH terms: Rituximab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 187.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Lymphoma, Non-Hodgkin's Lymphoma, Diffuse Large B-Cell Lymphoma, DLBCL, B-Cell Malignancy, anti-CD19, monoclonal antibody, second line, ASCT, Refractory

Summary:

      The overall purpose of the study is to determine if MEDI-551, when used in combination with
      salvage chemotherapy, Ifosfamide-carboplatin-etoposide (ICE) or Dexamethasone-cytarabine
      (DHAP) in patients with relapsed or refractory DLBCL who are eligible for Autologous Stem
      Cell Transplant (ASCT), has superior efficacy compared to rituximab in the same population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed aggressive B-cell DLBCL, including FL transforming to DLBCL &
             Grade III FL

          -  Relapsed from or refractory to at least one treatment containing rituximab or another
             anti-CD20 based immunotherapy combined with anthracycline- or anthracenedione-based
             chemotherapy

          -  Eligible for ASCT

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

          -  Life expectancy of ≥ 12 weeks

          -  Adequate hematological function

        Exclusion Criteria:

          -  Any chemotherapy, radiotherapy, immunotherapy, biologic, investigational or hormonal
             therapy for treatment of lymphoma within 28 days prior to treatment

          -  Previous cancer therapy for DLBCL other than anthracycline- or anthracenedione based
             chemoimmunotherapy, monotherapy rituximab prior to first line therapy and/or as a
             maintenance therapy, or limited field radiotherapy

          -  Prior autologous or allogeneic SCT

          -  New York Heart Association ≥ Class II congestive heart failure; Clinically significant
             abnormality on ECG

          -  History of other invasive malignancy within 5 years except for localized/in situ,
             carcinomas such as cervical carcinoma in situ.

          -  Evidence of active infection

          -  Documented current central nervous system involvement by leukemia or lymphoma