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

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

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.

Study Overview

• Status: Terminated
• Conditions: Diffuse, Large B-Cell, Lymphoma; Follicular Lymphoma, Grade 3b; Transformed Lymphoma / DLBCL
• Intervention / Treatment: Drug: denintuzumab mafodotin; Drug: rituximab; Drug: cyclophosphamide; Drug: doxorubicin; Drug: vincristine; Drug: prednisone

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).

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Ponce Medical School Foundation
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • Saint Bernards Cancer Center
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Fountain Valley, California, United States, 92708
      • Compassionate Cancer Care Medical Group, Inc.
    • San Francisco, California, United States, 94115
      • Pacific Hematology Oncology Associates
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • University of Colorado Health Memorial Hospital
    • Fort Collins, Colorado, United States, 80528
      • Poudre Valley Hospital Harmony Campus
  • Georgia
    • Macon, Georgia, United States, 31201
      • Central Georgia Cancer Care
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute
    • Mount Sterling, Kentucky, United States, 40353
      • Montgomery Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70122
      • Tulane University Hospital and Clinic
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic (Forrest General Hospital)
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • Research Medical Center
  • New Mexico
    • Farmington, New Mexico, United States, 87401
      • San Juan Oncology Associates
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center - Bronx
    • New York, New York, United States, 10029
      • Mount Sinai Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Wilson, North Carolina, United States, 27893
      • Regional Medical Oncology Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center Research
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Seidman Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Hollings Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology / Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Health - Baylor University Medical Center
    • Lubbock, Texas, United States, 79410
      • Joe Arrington Cancer Research and Treatment Center
    • Temple, Texas, United States, 76508
      • Scott and White Memorial Hospital - Temple
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Olympia, Washington, United States, 98502
      • Vista Oncology Inc PS
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties, PLLC

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:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: denintuzumab mafodotin + RCHOP; Part A: denintuzumab mafodotin (SGN-CD19A) + RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)	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; Drug: rituximab; 375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: cyclophosphamide; 750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: doxorubicin; 50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: vincristine; 1.4 mg/m2 every 3 weeks by IV infusion for up to 6 cycles (dose capped at 2 mg total); Drug: prednisone; 100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles
EXPERIMENTAL: denintuzumab mafodotin + RCHP; Part A: denintuzumab mafodotin (SGN-CD19A) + RCHP (rituximab, cyclophosphamide, doxorubicin, and prednisone)	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; Drug: rituximab; 375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: cyclophosphamide; 750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: doxorubicin; 50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: prednisone; 100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles
EXPERIMENTAL: denintuzumab mafodotin + RCHOP or RCHP; Part B: denintuzumab mafodotin (SGN-CD19A) + RCHOP or RCHP	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; Drug: rituximab; 375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: cyclophosphamide; 750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: doxorubicin; 50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: vincristine; 1.4 mg/m2 every 3 weeks by IV infusion for up to 6 cycles (dose capped at 2 mg total); Drug: prednisone; 100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles
ACTIVE_COMPARATOR: RCHOP; Part B: RCHOP alone: (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)	Drug: rituximab; 375 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: cyclophosphamide; 750 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: doxorubicin; 50 mg/m2 every 3 weeks by IV infusion for up to 6 cycles; Drug: vincristine; 1.4 mg/m2 every 3 weeks by IV infusion for up to 6 cycles (dose capped at 2 mg total); Drug: prednisone; 100 mg on Days 1 to 5 of each 3-week cycle, orally for up to 6 cycles

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B Outcome Measure: Complete Response Rate (CR)	Study did not progress to Part B.	N/A - Endpoint not assessed
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free Survival (EFS) Between Study Arms in Part B	Study did not progress to Part B	N/A - Endpoint not assessed
Progression-free Survival (PFS) Between Study Arms in Part B	Study did not progress to Part B.	N/A - Endpoint not assessed
Overall Survival (OS) Between Study Arms in Part B	Study did not progress to Part B.	N/A - Endpoint not assessed
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
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (ACTUAL): January 1, 2018
• Study Completion (ACTUAL): May 15, 2018

Study Registration Dates

• First Submitted: July 28, 2016
• First Submitted That Met QC Criteria: August 1, 2016
• First Posted (ESTIMATE): August 4, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 11, 2019
• Last Update Submitted That Met QC Criteria: February 11, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Drug Therapy; Immune System Diseases; DLBCL; Neoplasms; Immunotherapy; Lymphoma; Rituximab; Lymphoma, Non-Hodgkin; Cyclophosphamide; Hematologic Diseases; Doxorubicin; Antibody-Drug Conjugate; Antineoplastic Agents; Glucocorticoids; Vincristine; Antibodies, Monoclonal; Prednisone; Liposomal doxorubicin; Lymphoma, B-Cell; Immunoproliferative Disorders; Lymphatic Diseases; Neoplasms by Histologic Type; Antimitotic Agents; immunosuppressive agents; Anti-Inflammatory Agents; Lymphoma, Large B-Cell, Diffuse; Alkylating Agents; Antineoplastic Agents, Alkylating; SGN-19A; Denintuzumab Mafodotin; Antigens, CD19; Monomethyl auristatin F; Transformed Lymphoma / DLBCL; Antibiotic, Antineoplastic; Phytogenic Antirheumatic Agents; Follicular Lymphoma Grade 3b
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Rituximab; Prednisone; Doxorubicin; Vincristine
• Other Study ID Numbers: SGN19A-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO