Phase II Study of Ofatumumab Plus Ifosfamide, Carboplatin, Etoposide (ICE) or Dexamethasone, Cytarabine, Cisplatin (DHAP) Chemotherapy Regimen in Relapsed/ Refractory Diffuse Large B Cell Lymphoma (DLBCL)
Condition: Lymphoma, Large-Cell, Diffuse
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse
Intervention: ofatumumab + ICE; ofatumumab + DHAP
Intervention description: 3 cycles of treatment will be administered. Each cycle will last 21 days. ofatumumab dose: cycle 1, day 1 - 1000 milligrams (mg); cycle 1, day 8 - 1000 mg; cycle 2, day 1 and cycle 3, day 1 - 1000 mg
ICE regimen:
ifosfamide + mesna - 5 grams (g)/meters squared (m^2)/24 hours (hrs) continuous on day 2 of dosing cycle; carboplatin - AUC 5 (800 mg maximum) on day 2 of dosing cycle; etoposide - 100 mg/m^2 on days 1, 2 and 3 of dosing cycle.; 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/m^2/24 hrs continuous on day 1 of dosing cycle; cytarabine - 2 g/m^2 q12 hrs (2 doses) on day 2 of dosing cycle.
Intervention MeSH terms: Ofatumumab; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Salvage chemotherapy; relapsed; grade 3B follicular lymphoma; efficacy; safety; DHAP; ofatumumab; refractory; Non-Hodgkin's Lymphoma; Diffuse Large B Cell Lymphoma (DLBCL); Oncology; ICE; Transformed follicular lymphoma

Summary:

      The purpose of this study is to evaluate the safety and efficacy of ofatumumab used in
      combination with ifosfamide, carboplatin, etoposide (ICE) or dexamethasone, cytarabine,
      cisplatin (DHAP) salvage chemotherapy regimens in subjects with relapsed or refractory
      diffuse large B cell lymphoma (DLBCL) who are eligible for autologous stem cell transplant.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with CD20 positive aggressive non-Hodgkin's lymphoma (NHL) including DLBCL,
             transformed follicular lymphoma (FL) & grade 3b FL.

        Refractory to, or relapsed following, first-line treatment with rituximab combined with
        anthracycline- or anthracenedione-based chemotherapy as defined by the protocol.

          -  Computed tomography (CT) with involvement of 2 or more clearly demarcated lesions with
             a long axis > 1.5 centimeters (cm) and short axis ≥ 1.0 cm or 1 clearly demarcated
             lesion with a long axis >2.0 cm and short axis ≥1.0 cm.

          -  Baseline [18F] fluorodeoxyglucose (FDG)-positron emission tomography (PET) scans must
             demonstrate positive lesions compatible with CT defined anatomical tumor sites.

          -  Age 18 yrs or older.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

          -  Eligible for high dose chemotherapy and autologous stem cell transplant (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 required rituximab/
             anthracycline- or anthracenedione-based chemotherapy, monotherapy rituximab prior to
             first-line therapy and / or as a maintenance therapy, or limited field radiotherapy
             (as defined by the protocol).

          -  Any anti-cancer therapy, except limited field radiotherapy, within 2 weeks prior to
             start of study therapy.

          -  Chronic Glucocorticoid use (limited acute use is allowed and defined by the protocol).

          -  History of significant cerebrovascular disease.

          -  Abnormal/ inadequate white blood cell (WBC) count, liver, and kidney function.

          -  Clinically significant cardiac disease, active or chronic infections, serious
             significant diseases, other cancer within last 5 years.

          -  Known or suspected hypersensitivity to study treatments.

          -  Prior treatment with anti-CD20 monoclonal antibodies, at any time, or treated with
             other monoclonal antibodies within 3 months prior to start of study therapy, with the
             exception of rituximab in both instances.

          -  Inability to comply with the protocol activities.

          -  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.