Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy Followed by Autologous Stem Cell Transplant in Relapsed or Refractory Diffuse Large B Cell Lymphoma
Condition: Lymphoma, Large-Cell, Diffuse
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse
Intervention: OFATUMUMAB + DHAP; RITUXIMAB + DHAP
Intervention description: 3 cycles of treatment will be administered. Each cycle will last 21 days. ofatumumab dose: cycle 1, day 1 - 1000 mg; cycle 1, day 8 - 1000 mg; cycle 2, day 1 and cycle 3, day 1 - 1000 mg. DHAP regimen: dexamethasone - 40 mg on days 1, 2, 3, and 4 of dosing cycle; cisplatin - 100 mg/m2/24hrs continuous on day 1 of dosing cycle; cytarabine - 2g/m2 q12 hrs (2 doses) on day 2 of dosing cycle.; 3 cycles of treatment will be administered. Each cycle will last 21 days. rituximab dose: cycle 1, day 1 - 375 mg/m2; cycle 1, day 8 - 375 mg/m2; cycle 2, day 1 and cycle 3, day 1 - 375 mg/m2. DHAP regimen: dexamethasone - 40 mg on days 1, 2, 3, and 4 of dosing cycle; cisplatin - 100 mg/m2/24hrs continuous on day 1 of dosing cycle; cytarabine - 2g/m2 q12 hrs (2 doses) on day 2 of dosing cycle.
Intervention MeSH terms: Rituximab; Ofatumumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 447.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: The All Ireland Cooperative Oncology Research Group; GELTAMO; National Cancer Research Institute Lymphoma Clinical Studies Group; Genmab; ofatumumab; Japan Clinical Oncology Group; Oncology; Polish Lymphoma Research Group; Salvage chemotherapy; refractory; HOVON; DVD; relapsed; safety; efficacy; DHAP; rituximab; Autologous Stem Cell Transplant; Dutch-Belgian Cooperative Trial Group for Hematology-Oncology; Grupo Espanol de Linfomas; Nordic Lymphoma Group

Summary:

      This study is being conducted to compare the efficacy and safety of ofatumumab in addition to
      salvage chemotherapy versus rituximab in addition to salvage chemotherapy in CD20 positive
      DLBCL subjects relapsing, or with persistent disease, after first-line treatment with
      rituximab combined with an anthracycline-based chemotherapy regimen and be eligible for ASCT.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with CD20 positive DLBCL or grade 3b follicular lymphoma (FL) at original
             diagnosis.

          -  Refractory to, or relapsed following, first-line treatment with rituximab combined
             with anthracycline- or anthracenedione-based chemotherapy as defined by the protocol.

          -  CT with involvement of 2 or more clearly demarcated lesions/ nodes with a long axis >
             1.5 cm and short axis >= 1.0cm or 1 clearly demarcated lesion/ node with a long axis >
             2.0 cm and short axis >= 1.0 cm.

          -  Baseline FDG-PET scans must demonstrate positive lesions compatible with CT defined
             anatomical tumor sites.

          -  Age 18 yrs or older.

          -  ECOG performance status of 0, 1 or 2.

          -  Eligible for high dose chemotherapy and ASCT.

          -  Resolution of toxicities from first-line therapy to a grade that in the opinion of the
             investigator does not contraindicate study participation.

          -  Signed written informed consent.

        Exclusion Criteria:

          -  Previous cancer therapy for lymphoma, with the exception of first-line rituximab/
             anthracycline- or anthracenedione-based chemotherapy, monotherapy rituximab prior to
             or combined with first-line chemotherapy, as maintenance therapy, and radiotherapy in
             a limited field or as a part of the first-line treatment plan.

          -  Any anti-cancer therapy, except limited field radiotherapy, within 2 weeks prior to
             start of study therapy.

          -  Planned post-randomization chronic glucocorticoid use (limited acute use is allowed
             and defined by the protocol) unless administered as therapy for mild COPD or asthma.

          -  Clinically significant cardiac disease, active or chronic infections, serious
             significant diseases, other cancer within last 5 years. History of significant
             cerebrovascular disease.

          -  Prior treatment with anti-CD20 monoclonal antibodies with the exception of rituximab.

          -  Abnormal/ inadequate WBC count, liver, and kidney function.

          -  Pregnant or lactating women or female patients of child-bearing potential (or male
             patients with such partners) not willing to use adequate contraception during and up
             to 1 year following dosing completion.