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

Primary Purpose

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

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
denintuzumab mafodotin
rituximab
ifosfamide
carboplatin
etoposide
Sponsored by
Seagen Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma, B-cell focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Arkansas for Medical Sciences
  • City of Hope National Medical Center
  • Scripps Mercy Cancer Center
  • Colorado Blood Cancer Institute
  • Yale Cancer Center
  • Shands Cancer Center / University of Florida
  • University of Miami
  • H. Lee Moffitt Cancer Center & Research Institute
  • Winship Cancer Institute / Emory University School of Medicine
  • Rush University Medical Center
  • University of Chicago
  • Cardinal Bernardin Cancer Center / Loyola University Medical Center
  • University of Kansas Cancer Center
  • Beth Israel Deaconess Medical Center
  • Dana Farber Cancer Institute
  • University of Minnesota
  • Washington University School of Medicine
  • Hackensack University Medical Center
  • University of New Mexico Cancer Center
  • Memorial Sloan Kettering Cancer Center
  • UNC Lineberger Comprehensive Cancer Center / University of North Carolina
  • Levine Cancer Institute
  • Duke University Medical Center
  • MD Anderson Cancer Center / University of Texas
  • San Antonio Military Medical Center
  • University of Virginia
  • Seattle Cancer Care Alliance / University of Washington
  • Carbone Cancer Center / University of Wisconsin
  • Medical College of Wisconsin (Milwaukee)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

19A+RICE

RICE

Arm Description

Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide

Rituximab, ifosfamide, carboplatin, and etoposide

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
October 29, 2015
Last Updated
April 19, 2019
Sponsor
Seagen Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02592876
Brief Title
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

2. Study Status

Record Verification Date
April 2019
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision based on portfolio prioritization
Study Start Date
October 2015 (Actual)
Primary Completion Date
April 20, 2018 (Actual)
Study Completion Date
April 20, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Seagen Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
81 (Actual)

8. Arms, Groups, and Interventions

Arm Title
19A+RICE
Arm Type
Experimental
Arm Description
Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide
Arm Title
RICE
Arm Type
Active Comparator
Arm Description
Rituximab, ifosfamide, carboplatin, and etoposide
Intervention Type
Drug
Intervention Name(s)
denintuzumab mafodotin
Other Intervention Name(s)
SGN-CD19A
Intervention Description
Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.
Intervention Type
Drug
Intervention Name(s)
rituximab
Intervention Description
375 mg/m^2 by IV infusion, every 3 weeks for up to 3 cycles
Intervention Type
Drug
Intervention Name(s)
ifosfamide
Intervention Description
5000 mg/m^2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Description
AUC 5mg/mL x min by IV infusion, every 3 weeks for up to 3 cycles
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Description
100 mg/m^2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles
Primary Outcome Measure Information:
Title
Complete Remission Rate Per Independent Review Facility
Description
Number of patients with complete metabolic response by PET (positive emission tomography) and CT (computed tomography) scans, or complete radiologic response by CT only.
Time Frame
Up to 4 months
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events (AEs)
Description
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.
Time Frame
Up to 4 months
Title
Number of Participants With Laboratory Abnormalities
Description
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).
Time Frame
Up to 4 months
Title
Objective Response Rate (ORR)
Description
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.
Time Frame
Up to 4 months
Title
Duration of Complete Response (CR)
Description
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.
Time Frame
Up to 27.9 months
Title
Duration of Objective Response (OR)
Description
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.
Time Frame
Up to 27.9 months
Title
Progression-free Survival (PFS)
Description
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.
Time Frame
Up to 30 months
Title
Overall Survival (OS)
Description
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.
Time Frame
Up to 30 months
Title
Number of Patients Achieving Peripheral Blood Stem Cell (PBSC) Mobilization
Description
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.
Time Frame
Up to 30 months
Title
Number of Patients Receiving Autologous Stem Cell Transplant (ASCT)
Description
Number of patients receiving ASCT after completion of study treatment (EOT), prior to subsequent anticancer therapy.
Time Frame
Up to 30 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Juan Pinelli, PA-C, MMSc
Organizational Affiliation
Seagen Inc.
Official's Role
Study Director
Facility Information:
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
City of Hope National Medical Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010-3000
Country
United States
Facility Name
Scripps Mercy Cancer Center
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Yale Cancer Center
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06520
Country
United States
Facility Name
Shands Cancer Center / University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
H. Lee Moffitt Cancer Center & Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Winship Cancer Institute / Emory University School of Medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637-1470
Country
United States
Facility Name
Cardinal Bernardin Cancer Center / Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
University of Kansas Cancer Center
City
Westwood
State/Province
Kansas
ZIP/Postal Code
United States
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
University of New Mexico Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87106
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
UNC Lineberger Comprehensive Cancer Center / University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Levine Cancer Institute
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28204
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
MD Anderson Cancer Center / University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4095
Country
United States
Facility Name
San Antonio Military Medical Center
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78234
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Facility Name
Seattle Cancer Care Alliance / University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109-1023
Country
United States
Facility Name
Carbone Cancer Center / University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
United States
Country
United States
Facility Name
Medical College of Wisconsin (Milwaukee)
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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