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

NCT02592876 | Terminated Phase 2 Results

• 1 other identifier: SGN19A-003
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 29

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.

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Number of Participants With Adverse Events (AEs)

  Up to 4 months

• Number of Participants With Laboratory Abnormalities

  Up to 4 months

• Objective Response Rate (ORR)

  Up to 4 months

• Duration of Complete Response (CR)

  Up to 27.9 months

• Duration of Objective Response (OR)

  Up to 27.9 months

Study Arms (2)

19A+RICE

EXPERIMENTAL

Denintuzumab mafodotin plus rituximab, ifosfamide, carboplatin, and etoposide

Drug: denintuzumab mafodotin; Drug: rituximab; Drug: ifosfamide; Drug: carboplatin; Drug: etoposide

RICE

ACTIVE COMPARATOR

Rituximab, ifosfamide, carboplatin, and etoposide

Drug: rituximab; Drug: ifosfamide; Drug: carboplatin; Drug: etoposide

Interventions

denintuzumab mafodotin DRUG

Denintuzumab mafodotin 3 mg/kg by intravenous (IV) infusion, every 3 weeks for up to 3 cycles.

Also known as: SGN-CD19A

19A+RICE

rituximab DRUG

375 mg/m\^2 by IV infusion, every 3 weeks for up to 3 cycles

19A+RICE; RICE

ifosfamide DRUG

5000 mg/m\^2 by IV infusion over a 24-hour period, every 3 weeks for up to 3 cycles

19A+RICE; RICE

carboplatin DRUG

AUC 5mg/mL x min by IV infusion, every 3 weeks for up to 3 cycles

19A+RICE; RICE

etoposide DRUG

100 mg/m\^2 per day by IV infusion for 3 days, every 3 weeks for up to 3 cycles

19A+RICE; RICE

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seagen Inc.: lead

Study Sites (29)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

City of Hope National Medical Center

Duarte, California, 91010-3000, United States

Location

Scripps Mercy Cancer Center

San Diego, California, 92103, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

Shands Cancer Center / University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute / Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago

Chicago, Illinois, 60637-1470, United States

Location

Cardinal Bernardin Cancer Center / Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, United States, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

UNC Lineberger Comprehensive Cancer Center / University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MD Anderson Cancer Center / University of Texas

Houston, Texas, 77030-4095, United States

Location

San Antonio Military Medical Center

San Antonio, Texas, 78234, United States

Location

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Seattle Cancer Care Alliance / University of Washington

Seattle, Washington, 98109-1023, United States

Location

Carbone Cancer Center / University of Wisconsin

Madison, Wisconsin, United States, United States

Location

Medical College of Wisconsin (Milwaukee)

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma; Lymphoma, Follicular; Hematologic Diseases; Immune System Diseases; Immunoproliferative Disorders; Lymphatic Diseases; Lymphoma, Non-Hodgkin; Neoplasms; Neoplasms by Histologic Type

Interventions

Rituximab; Ifosfamide; Carboplatin; Etoposide

Condition Hierarchy (Ancestors)

Lymphoproliferative Disorders; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Seattle Genetics, Inc.

medinfo@seagen.com

(855)473-2436

Study Officials

• Juan Pinelli, PA-C, MMSc

  Seagen Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2015
• First Posted: October 30, 2015
• Study Start: October 1, 2015
• Primary Completion: April 20, 2018
• Study Completion: April 20, 2018
• Last Updated: May 17, 2019
• Results First Posted: May 17, 2019

Record last verified: 2019-04

Locations

US (29)