Treatment Study of Denintuzumab Mafodotin (SGN-CD19A) Plus RICE Versus RICE Alone for Diffuse Large B-Cell Lymphoma
- Conditions
- Lymphoma, B-cellLymphoma, Large B-Cell, DiffuseLymphoma, Follicular, Grade 3bFollicular Lymphoma, Grade 3b
- Interventions
- Registration Number
- NCT02592876
- Lead Sponsor
- Seagen Inc.
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 81
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 19A+RICE denintuzumab mafodotin Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide 19A+RICE carboplatin Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide RICE rituximab Rituximab, ifosfamide, carboplatin, and etoposide 19A+RICE etoposide Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide 19A+RICE rituximab Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide 19A+RICE ifosfamide Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide RICE ifosfamide Rituximab, ifosfamide, carboplatin, and etoposide RICE carboplatin Rituximab, ifosfamide, carboplatin, and etoposide RICE etoposide Rituximab, ifosfamide, carboplatin, and etoposide
- Primary Outcome Measures
Name Time Method Complete Remission Rate Per Independent Review Facility Up to 4 months Number of patients with complete metabolic response by PET (positive emission tomography) and CT (computed tomography) scans, or complete radiologic response by CT only.
- Secondary Outcome Measures
Name Time Method Number of Patients Achieving Peripheral Blood Stem Cell (PBSC) Mobilization Up to 30 months Defined as the number of patients who are able to adequately mobilize PBSC per investigator assessment on or after completion of study treatment, prior to subsequent anticancer therapy.
Number of Participants With Adverse Events (AEs) Up to 4 months Treatment-emergent adverse events (TEAEs) are presented and defined as newly occurring (not present at baseline) or worsening after first dose of investigational product. AE severity and seriousness are assessed independently. 'Severity' characterizes the intensity of an AE and is graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. An AE is considered 'serious' if it is life-threatening, fatal, requires hospitalization, or is otherwise considered to be medically significant.
Number of Participants With Laboratory Abnormalities Up to 4 months Number of participants who experienced a maximum post-baseline laboratory toxicity of Grade 3 or higher (per National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03).
Objective Response Rate (ORR) Up to 4 months ORR is defined as the proportion of patients with complete remission (CR) or partial remission (PR) per independent review facility (IRF) at the end of treatment.
Duration of Complete Response (CR) Up to 27.9 months Defined as the time from the start of the first radiographic documentation of CR per investigator to the first documentation of progressive disease, death due to any cause, or receipt of subsequent anticancer therapy, whichever comes first.
Duration of Objective Response (OR) Up to 27.9 months Duration of OR is defined as the time from the start of the first radiographic documentation of OR per investigator to the first documentation of PD, death due to any cause, or receipt of subsequent anticancer therapy, whichever comes first.
Progression-free Survival (PFS) Up to 30 months PFS is defined as the time from randomization to first documentation of disease progression per investigator, death due to any cause, or receipt of subsequent anticancer therapy, whichever comes first.
Overall Survival (OS) Up to 30 months OS is defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time will be censored at the last date the patient is known to be alive.
Number of Patients Receiving Autologous Stem Cell Transplant (ASCT) Up to 30 months Number of patients receiving ASCT after completion of study treatment (EOT), prior to subsequent anticancer therapy.
Trial Locations
- Locations (29)
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
University of Chicago
🇺🇸Chicago, Illinois, United States
University of Kansas Cancer Center
🇺🇸Westwood, Kansas, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Shands Cancer Center / University of Florida
🇺🇸Gainesville, Florida, United States
University of New Mexico Cancer Center
🇺🇸Albuquerque, New Mexico, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Levine Cancer Institute
🇺🇸Charlotte, North Carolina, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
Winship Cancer Institute / Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Cardinal Bernardin Cancer Center / Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Carbone Cancer Center / University of Wisconsin
🇺🇸Madison, Wisconsin, United States
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
Scripps Mercy Cancer Center
🇺🇸San Diego, California, United States
Colorado Blood Cancer Institute
🇺🇸Denver, Colorado, United States
University of Miami
🇺🇸Miami, Florida, United States
H. Lee Moffitt Cancer Center & Research Institute
🇺🇸Tampa, Florida, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
San Antonio Military Medical Center
🇺🇸San Antonio, Texas, United States
MD Anderson Cancer Center / University of Texas
🇺🇸Houston, Texas, United States
Medical College of Wisconsin (Milwaukee)
🇺🇸Milwaukee, Wisconsin, United States
Seattle Cancer Care Alliance / University of Washington
🇺🇸Seattle, Washington, United States
UNC Lineberger Comprehensive Cancer Center / University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States