Treatment Study of Denintuzumab Mafodotin (SGN-CD19A) Plus RICE Versus RICE Alone for Diffuse Large B-Cell Lymphoma
Condition: Lymphoma, B-cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular, Grade 3b; Follicular Lymphoma, Grade 3b
MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: denintuzumab mafodotin; rituximab; ifosfamide; carboplatin; etoposide
Intervention description: Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.; 375 mg/m^2 by IV infusion, every 3 weeks for up to 3 cycles; 5000 mg/m^2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles; AUC 5mg/mL x min by IV infusion, every 3 weeks for up to 3 cycles; 100 mg/m^2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
Intervention MeSH terms: Rituximab; Carboplatin; Etoposide; Ifosfamide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 81.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Antibodies, Monoclonal; Antibody-Drug Conjugate; Antigens, CD19; Autologous Stem Cell Transplant; Drug Therapy; Follicular Lymphoma Grade 3b; Hematologic Diseases; Immune System Diseases; Immunoproliferative Disorders; Immunotherapy; Lymphatic Diseases; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Monomethylauristatin F; Neoplasms; Neoplasms by Histologic Type; Transformed Lymphoma / DLBCL; Rituximab; Ifosfamide; Carboplatin; Etoposide

Summary:

      The purpose of this randomized, open-label study is to evaluate the safety and efficacy of
      denintuzumab mafodotin plus RICE (rituximab, ifosfamide, carboplatin, and etoposide) when
      compared to RICE alone in the treatment of patients with relapsed or refractory diffuse large
      B-cell lymphoma (DLBCL) or Grade 3b follicular lymphoma. Eligible patients must also be
      candidates for autologous stem cell transplant. Patients will be randomly assigned in a 1:1
      ratio to receive 3 cycles of study treatment with either denintuzumab mafodotin + RICE or
      RICE alone. The study will assess whether there is a difference between the 2 groups in the
      side effects that are reported and the number of patients who achieve complete remission at
      the end of their study treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Pathologically confirmed diagnosis of relapsed or refractory diffuse large B-cell
             lymphoma (DLBCL; including de novo and transformed DLBCL) or Grade 3b follicular
             lymphoma

          -  Available representative tissue from the most recent biopsy after the last therapy; if
             such tissue is not available, a fresh biopsy must be obtained

          -  Received only frontline CD20-directed immunotherapy with anthracycline- or
             anthracenedione-based multi-agent chemotherapy. Monotherapy rituximab or other
             CD20-directed immunotherapy as maintenance therapy prior to frontline chemotherapy,
             and radiotherapy in a limited field or as part of the frontline treatment plan are
             permitted.

          -  Achieved a response of stable disease, partial response, or complete response
             following the last cycle of frontline treatment. In addition, patients must have
             relapsed less than or equal to 6 months from the completion of frontline therapy at
             the time of initial dosing in this clinical trial.

          -  Considered eligible for high-dose chemotherapy followed by autologous stem cell
             transplant (ASCT)

          -  Fluorodeoxyglucose (FDG)-avid disease by positive emission tomography (PET), and
             measurable disease greater than 1.5 cm in diameter

          -  Eastern Cooperative Oncology Group (ECOG) performance less than or equal to 2

          -  Adequate kidney and hematologic function assessed from baseline laboratory data

        Exclusion Criteria:

          -  Previous history of indolent lymphoma treated with more than 1 multi-agent
             chemotherapy regimen or previous cancer therapy for recurrent DLBCL or Grade 3b
             follicular lymphoma

          -  History of autologous or allogeneic stem cell transplant

          -  History of another primary invasive cancer, hematologic malignancy, or myelodysplastic
             syndrome that has not been in remission for at least 1 year

          -  History of progressive multifocal leukoencephalopathy (PML)

          -  Cerebral/meningeal disease related to the underlying malignancy that has not been
             definitively treated

          -  Known urinary tract obstruction

          -  Patients with the following ocular conditions: corneal disorders, monocular vision
             (i.e., best corrected visual acuity greater than or equal to 20/200 in one eye), or
             active ocular disorders requiring treatment