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

Diffuse, Large B-Cell, Lymphoma Clinical Trial

Official title:

An Open Label Phase 2 Study of Denintuzumab Mafodotin (SGN-CD19A) in Combination With RCHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone) or RCHP (Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone) Compared With RCHOP Alone as Frontline Therapy in Patients With Diffuse Large B-cell Lymphoma (DLBCL) or Follicular Lymphoma (FL) Grade 3b

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02855359
• Other study ID #: SGN19A-004
• Status: Terminated
• Phase: Phase 2
• Start date: August 2016
• Est. completion date: May 15, 2018

Study information

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

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: May 15, 2018
• Est. primary completion date: January 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• denintuzumab mafodotin
SGN-CD19A at 3 mg/kg will be administered every 6 weeks via intravenous (IV) infusion, up to a maximum of three (3) doses, on Day 1 of Cycles 1, 3, and 5 of 21-day cycles
• rituximab
375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
• cyclophosphamide
750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
• doxorubicin
50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles
• vincristine
1.4 mg/m2 every 3 weeks by IV infusion for up to 6 cycles (dose capped at 2 mg total)
• prednisone
100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Seattle Genetics, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part B Outcome Measure: Complete Response Rate (CR)	Study did not progress to Part B.	N/A - Endpoint not assessed
Primary	Part A and Part B Outcome Measure: Incidence of Adverse Events	Part A data only; study did not progress to Part B.	54.7 weeks
Primary	Part A and Part B Outcome Measure: Incidence of Laboratory Abnormalities	Part A data reported; study did not progress to Part B. Laboratory abnormalities Grade 1+ are reported.	Up to 183 days
Secondary	Event-free Survival (EFS) Between Study Arms in Part B	Study did not progress to Part B	N/A - Endpoint not assessed
Secondary	Progression-free Survival (PFS) Between Study Arms in Part B	Study did not progress to Part B.	N/A - Endpoint not assessed
Secondary	Overall Survival (OS) Between Study Arms in Part B	Study did not progress to Part B.	N/A - Endpoint not assessed
Secondary	Objective Response Rate (ORR) at End Of Treatment (EOT) Between Study Arms in Part B	Study did not progress to Part B.	N/A - Endpoint not assessed
Secondary	Duration of Objective Response and of Complete Response (CR) Between Study Arms in Part B	Study did not progress to Part B.	N/A - Endpoint not assessed