Denintuzumab Mafodotin (SGN-CD19A) Combined With RCHOP or RCHP Versus RCHOP Alone in Diffuse Large B-Cell Lymphoma or Follicular Lymphoma

Phase 2

Terminated

Conditions: Transformed Lymphoma / DLBCL
Diffuse, Large B-Cell, Lymphoma
Follicular Lymphoma, Grade 3b

Interventions: Drug: denintuzumab mafodotin
Drug: rituximab
Drug: cyclophosphamide
Drug: doxorubicin
Drug: vincristine
Drug: prednisone

Registration Number: NCT02855359

Lead Sponsor: Seagen Inc.

Brief Summary: This is a Phase 2 study to evaluate the combination of denintuzumab mafodotin in combination with RCHOP or RCHP compared with RCHOP alone as front-line therapy in patients with diffuse large B-cell lymphoma or follicular lymphoma Grade 3b.

Detailed Description: In Part A of the study, patients will be randomized 1:1 to receive denintuzumab mafodotin plus RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) or denintuzumab mafodotin plus RCHP (rituximab, cyclophosphamide, doxorubicin, and prednisone) to assess the safety of these 2 combination regimens. Part B of the study is designed to evaluate the antitumor activity and safety of denintuzumab mafodotin in combination with either RCHOP or RCHP (Experimental Arm) compared with RCHOP alone (Comparator Arm).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 24

Inclusion Criteria

Treatment-naive patients with histologically confirmed systemic de novo or transformed diffuse large B-cell lymphoma (DLBCL) (from follicular or marginal zone lymphoma), or follicular lymphoma (FL) Grade 3b;
- patients must have high intermediate or high risk disease
Tumor tissue available from most recent biopsy to determine cell of origin
Fluorodeoxyglucose-avid disease by positron emission tomography and measurable disease greater than 1.5cm diameter
Eastern Cooperative Oncology Group performance status ≤2
Age 18 years or older
Adequate study baseline laboratory parameters

Exclusion Criteria

Previous history of treated indolent lymphoma
History of another primary invasive cancer, hematologic malignancy, or myelodysplastic syndrome that has not been in remission for at least 3 years
History of progressive multifocal leukoencephalopathy
Cerebral/meningeal disease related to the underlying malignancy
Patients with the following ocular conditions: corneal disorders, monocular vision (ie. best corrected visual acuity greater than or equal to 20/200 in one eye), or active ocular disorders requiring treatment

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
denintuzumab mafodotin + RCHOP	rituximab	Part A: denintuzumab mafodotin (SGN-CD19A) + RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
denintuzumab mafodotin + RCHOP or RCHP	rituximab	Part B: denintuzumab mafodotin (SGN-CD19A) + RCHOP or RCHP
denintuzumab mafodotin + RCHOP	cyclophosphamide	Part A: denintuzumab mafodotin (SGN-CD19A) + RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
denintuzumab mafodotin + RCHOP	vincristine	Part A: denintuzumab mafodotin (SGN-CD19A) + RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
denintuzumab mafodotin + RCHOP	doxorubicin	Part A: denintuzumab mafodotin (SGN-CD19A) + RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
denintuzumab mafodotin + RCHOP	prednisone	Part A: denintuzumab mafodotin (SGN-CD19A) + RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
denintuzumab mafodotin + RCHP	cyclophosphamide	Part A: denintuzumab mafodotin (SGN-CD19A) + RCHP (rituximab, cyclophosphamide, doxorubicin, and prednisone)
denintuzumab mafodotin + RCHP	rituximab	Part A: denintuzumab mafodotin (SGN-CD19A) + RCHP (rituximab, cyclophosphamide, doxorubicin, and prednisone)
denintuzumab mafodotin + RCHP	doxorubicin	Part A: denintuzumab mafodotin (SGN-CD19A) + RCHP (rituximab, cyclophosphamide, doxorubicin, and prednisone)
denintuzumab mafodotin + RCHP	prednisone	Part A: denintuzumab mafodotin (SGN-CD19A) + RCHP (rituximab, cyclophosphamide, doxorubicin, and prednisone)
denintuzumab mafodotin + RCHOP or RCHP	doxorubicin	Part B: denintuzumab mafodotin (SGN-CD19A) + RCHOP or RCHP
RCHOP	rituximab	Part B: RCHOP alone: (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
RCHOP	cyclophosphamide	Part B: RCHOP alone: (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
denintuzumab mafodotin + RCHOP or RCHP	vincristine	Part B: denintuzumab mafodotin (SGN-CD19A) + RCHOP or RCHP
denintuzumab mafodotin + RCHOP or RCHP	cyclophosphamide	Part B: denintuzumab mafodotin (SGN-CD19A) + RCHOP or RCHP
denintuzumab mafodotin + RCHOP or RCHP	prednisone	Part B: denintuzumab mafodotin (SGN-CD19A) + RCHOP or RCHP
RCHOP	vincristine	Part B: RCHOP alone: (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
RCHOP	doxorubicin	Part B: RCHOP alone: (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
RCHOP	prednisone	Part B: RCHOP alone: (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
denintuzumab mafodotin + RCHOP	denintuzumab mafodotin	Part A: denintuzumab mafodotin (SGN-CD19A) + RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)
denintuzumab mafodotin + RCHP	denintuzumab mafodotin	Part A: denintuzumab mafodotin (SGN-CD19A) + RCHP (rituximab, cyclophosphamide, doxorubicin, and prednisone)
denintuzumab mafodotin + RCHOP or RCHP	denintuzumab mafodotin	Part B: denintuzumab mafodotin (SGN-CD19A) + RCHOP or RCHP

Primary Outcome Measures

Name	Time	Method
Part B Outcome Measure: Complete Response Rate (CR)	N/A - Endpoint not assessed	Study did not progress to Part B.
Part A and Part B Outcome Measure: Incidence of Adverse Events	54.7 weeks	Part A data only; study did not progress to Part B.
Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities	Up to 183 days	Part A data reported; study did not progress to Part B. Laboratory abnormalities Grade 1+ are reported.

Secondary Outcome Measures

Name	Time	Method
Event-free Survival (EFS) Between Study Arms in Part B	N/A - Endpoint not assessed	Study did not progress to Part B
Progression-free Survival (PFS) Between Study Arms in Part B	N/A - Endpoint not assessed	Study did not progress to Part B.
Overall Survival (OS) Between Study Arms in Part B	N/A - Endpoint not assessed	Study did not progress to Part B.
Objective Response Rate (ORR) at End Of Treatment (EOT) Between Study Arms in Part B	N/A - Endpoint not assessed	Study did not progress to Part B.
Duration of Objective Response and of Complete Response (CR) Between Study Arms in Part B	N/A - Endpoint not assessed	Study did not progress to Part B.

Trial Locations

Locations (35): Ponce Medical School Foundation
🇵🇷
Ponce, Puerto Rico
Hollings Cancer Center
🇺🇸
Charleston, South Carolina, United States
Northwest Medical Specialties, PLLC
🇺🇸
Tacoma, Washington, United States
City of Hope
🇺🇸
Duarte, California, United States
University of Colorado Health Memorial Hospital
🇺🇸
Colorado Springs, Colorado, United States
Poudre Valley Hospital Harmony Campus
🇺🇸
Fort Collins, Colorado, United States
University of Iowa Hospitals and Clinics
🇺🇸
Iowa City, Iowa, United States
Tulane University Hospital and Clinic
🇺🇸
New Orleans, Louisiana, United States
Montefiore Medical Center - Bronx
🇺🇸
Bronx, New York, United States
Research Medical Center
🇺🇸
Kansas City, Missouri, United States
Montgomery Cancer Center
🇺🇸
Mount Sterling, Kentucky, United States
San Juan Oncology Associates
🇺🇸
Farmington, New Mexico, United States
Kadlec Clinic Hematology and Oncology
🇺🇸
Kennewick, Washington, United States
Joe Arrington Cancer Research and Treatment Center
🇺🇸
Lubbock, Texas, United States
Vista Oncology INC PS
🇺🇸
Olympia, Washington, United States
Norton Cancer Institute
🇺🇸
Louisville, Kentucky, United States
Regional Medical Oncology Center
🇺🇸
Wilson, North Carolina, United States
Mount Sinai Hospital
🇺🇸
New York, New York, United States
Scott and White Memorial Hospital - Temple
🇺🇸
Temple, Texas, United States
University of Alabama at Birmingham
🇺🇸
Birmingham, Alabama, United States
Saint Bernards Cancer Center
🇺🇸
Jonesboro, Arkansas, United States
Pacific Hematology Oncology Associates
🇺🇸
San Francisco, California, United States
University of Michigan Comprehensive Cancer Center
🇺🇸
Ann Arbor, Michigan, United States
Virginia Piper Cancer Institute
🇺🇸
Minneapolis, Minnesota, United States
Hattiesburg Clinic (Forrest General Hospital)
🇺🇸
Hattiesburg, Mississippi, United States
Compassionate Cancer Care Medical Group, Inc.
🇺🇸
Fountain Valley, California, United States
Central Georgia Cancer Care
🇺🇸
Macon, Georgia, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
Gabrail Cancer Center Research
🇺🇸
Canton, Ohio, United States
University Hospitals Seidman Cancer Center
🇺🇸
Cleveland, Ohio, United States
Thomas Jefferson University Hospital
🇺🇸
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸
Pittsburgh, Pennsylvania, United States
Tennessee Oncology / Sarah Cannon Research Institute
🇺🇸
Nashville, Tennessee, United States
Baylor Health - Baylor University Medical Center
🇺🇸
Dallas, Texas, United States