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

Lymphoma, B-cell Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02592876
• Other study ID #: SGN19A-003
• Status: Terminated
• Phase: Phase 2
• Start date: October 2015
• Est. completion date: April 20, 2018

Study information

• Verified date: April 2019
• Source: Seattle Genetics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 81
• Est. completion date: April 20, 2018
• Est. primary completion date: April 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Follicular Lymphoma, Grade 3b
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Follicular
• Lymphoma, Follicular, Grade 3b
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• denintuzumab mafodotin
Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
• rituximab
375 mg/m^2 by IV infusion, every 3 weeks for up to 3 cycles
• ifosfamide
5000 mg/m^2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
• carboplatin
AUC 5mg/mL x min by IV infusion, every 3 weeks for up to 3 cycles
• etoposide
100 mg/m^2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Winship Cancer Institute / Emory University School of Medicine	Atlanta	Georgia
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	UNC Lineberger Comprehensive Cancer Center / University of North Carolina	Chapel Hill	North Carolina
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	City of Hope National Medical Center	Duarte	California
United States	Duke University Medical Center	Durham	North Carolina
United States	Shands Cancer Center / University of Florida	Gainesville	Florida
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center / University of Texas	Houston	Texas
United States	University of Arkansas for Medical Sciences	Little Rock	Arkansas
United States	Carbone Cancer Center / University of Wisconsin	Madison	Wisconsin
United States	Cardinal Bernardin Cancer Center / Loyola University Medical Center	Maywood	Illinois
United States	University of Miami	Miami	Florida
United States	Medical College of Wisconsin (Milwaukee)	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	San Antonio Military Medical Center	San Antonio	Texas
United States	Scripps Mercy Cancer Center	San Diego	California
United States	Seattle Cancer Care Alliance / University of Washington	Seattle	Washington
United States	H. Lee Moffitt Cancer Center & Research Institute	Tampa	Florida
United States	University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Seattle Genetics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Complete Remission Rate Per Independent Review Facility	Number of patients with complete metabolic response by PET (positive emission tomography) and CT (computed tomography) scans, or complete radiologic response by CT only.	Up to 4 months
Secondary	Number of Participants With Adverse Events (AEs)	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.	Up to 4 months
Secondary	Number of Participants With Laboratory Abnormalities	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).	Up to 4 months
Secondary	Objective Response Rate (ORR)	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.	Up to 4 months
Secondary	Duration of Complete Response (CR)	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.	Up to 27.9 months
Secondary	Duration of Objective Response (OR)	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.	Up to 27.9 months
Secondary	Progression-free Survival (PFS)	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.	Up to 30 months
Secondary	Overall Survival (OS)	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.	Up to 30 months
Secondary	Number of Patients Achieving Peripheral Blood Stem Cell (PBSC) Mobilization	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.	Up to 30 months
Secondary	Number of Patients Receiving Autologous Stem Cell Transplant (ASCT)	Number of patients receiving ASCT after completion of study treatment (EOT), prior to subsequent anticancer therapy.	Up to 30 months