Clinical trial NCT02592876: Treatment Study of Denintuzumab Mafodotin (SGN-CD19A) Plus RICE Versus RICE Alone for Diffuse Large B-Cell Lymphoma
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Lymphoma, B-cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Follicular, Grade 3b
Follicular Lymphoma, Grade 3b
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
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2015-10-30
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Complete Remission Rate Per Independent Review Facility
timeFrame: Up to 4 months
Secondary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 4 months
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Up to 4 months
measure: Objective Response Rate (ORR)
timeFrame: Up to 4 months
measure: Duration of Complete Response (CR)
timeFrame: Up to 27.9 months
measure: Duration of Objective Response (OR)
timeFrame: Up to 27.9 months
measure: Progression-free Survival (PFS)
timeFrame: Up to 30 months
measure: Overall Survival (OS)
timeFrame: Up to 30 months
measure: Number of Patients Achieving Peripheral Blood Stem Cell (PBSC) Mobilization
timeFrame: Up to 30 months
measure: Number of Patients Receiving Autologous Stem Cell Transplant (ASCT)
timeFrame: Up to 30 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: San Diego
country: United States
facility: Scripps Mercy Cancer Center
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Gainesville
country: United States
facility: Shands Cancer Center / University of Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute / Emory University School of Medicine
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center / Loyola University Medical Center
state: Illinois
city: Westwood
country: United States
facility: University of Kansas Cancer Center
state: Kansas
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: UNC Lineberger Comprehensive Cancer Center / University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: San Antonio
country: United States
facility: San Antonio Military Medical Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance / University of Washington
state: Washington
city: Madison
country: United States
facility: Carbone Cancer Center / University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin (Milwaukee)
state: Wisconsin
Study officials:
affiliation: Seagen Inc.
name: Juan Pinelli, PA-C, MMSc
role: STUDY_DIRECTOR
References: