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.

Study Overview

• Status: Terminated
• Conditions: Lymphoma, Large B-Cell, Diffuse; Follicular Lymphoma, Grade 3b; Lymphoma, B-cell; Lymphoma, Follicular, Grade 3b
• Intervention / Treatment: Drug: denintuzumab mafodotin; Drug: rituximab; Drug: ifosfamide; Drug: carboplatin; Drug: etoposide

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope National Medical Center
    • San Diego, California, United States, 92103
      • Scripps Mercy Cancer Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center
  • Florida
    • Gainesville, Florida, United States, 32610
      • Shands Cancer Center / University of Florida
    • Miami, Florida, United States, 33136
      • University of Miami
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center & Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute / Emory University School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637-1470
      • University of Chicago
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center / Loyola University Medical Center
  • Kansas
    • Westwood, Kansas, United States, United States
      • University of Kansas Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico Cancer Center
  • New York
    • New York, New York, United States, 10021
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Lineberger Comprehensive Cancer Center / University of North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Texas
    • Houston, Texas, United States, 77030-4095
      • MD Anderson Cancer Center / University of Texas
    • San Antonio, Texas, United States, 78234
      • San Antonio Military Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98109-1023
      • Seattle Cancer Care Alliance / University of Washington
  • Wisconsin
    • Madison, Wisconsin, United States, United States
      • Carbone Cancer Center / University of Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin (Milwaukee)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 19A+RICE; Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide	Drug: denintuzumab mafodotin; Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.; Other Names: SGN-CD19A; Drug: rituximab; 375 mg/m^2 by IV infusion, every 3 weeks for up to 3 cycles; Drug: ifosfamide; 5000 mg/m^2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles; Drug: carboplatin; AUC 5mg/mL x min by IV infusion, every 3 weeks for up to 3 cycles; Drug: etoposide; 100 mg/m^2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
Active Comparator: RICE; Rituximab, ifosfamide, carboplatin, and etoposide	Drug: rituximab; 375 mg/m^2 by IV infusion, every 3 weeks for up to 3 cycles; Drug: ifosfamide; 5000 mg/m^2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles; Drug: carboplatin; AUC 5mg/mL x min by IV infusion, every 3 weeks for up to 3 cycles; Drug: etoposide; 100 mg/m^2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Investigators: Study Director: Juan Pinelli, PA-C, MMSc, Seagen Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): April 20, 2018
• Study Completion (Actual): April 20, 2018

Study Registration Dates

• First Submitted: October 29, 2015
• First Submitted That Met QC Criteria: October 29, 2015
• First Posted (Estimate): October 30, 2015

Study Record Updates

• Last Update Posted (Actual): May 17, 2019
• Last Update Submitted That Met QC Criteria: April 19, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Drug Therapy; Immune System Diseases; Neoplasms; Immunotherapy; Lymphoma; Rituximab; Lymphoma, Non-Hodgkin; Carboplatin; Etoposide; Hematologic Diseases; Antibody-Drug Conjugate; Antibodies, Monoclonal; Lymphoma, B-Cell; Immunoproliferative Disorders; Lymphatic Diseases; Ifosfamide; Neoplasms by Histologic Type; Autologous Stem Cell Transplant; Lymphoma, Large B-Cell, Diffuse; Antigens, CD19; Transformed Lymphoma / DLBCL; Follicular Lymphoma Grade 3b; Monomethylauristatin F
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Carboplatin; Etoposide; Ifosfamide; Rituximab
• Other Study ID Numbers: SGN19A-003