Treatment Study of Denintuzumab Mafodotin (SGN-CD19A) Plus RICE Versus RICE Alone for Diffuse Large B-Cell Lymphoma

A Randomized, Open-Label Phase 2 Study of Denintuzumab Mafodotin (SGN-CD19A) Plus Rituximab, Ifosfamide, Carboplatin, and Etoposide (19A+RICE) Chemotherapy vs. RICE in the Treatment of Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) Who Are Candidates for Autologous Stem Cell Transplant

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.

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