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).

Study Timeline

• Study First Submitted: 2016-07-28
• Study Start: 2016-08
• Study First Submitted QC: 2016-08-01
• Study First Posted: 2016-08-04
• Primary Completion: 2018-01
• Study Completion: 2018-05-15
• Results First Submitted: 2018-12-18
• Results First Submitted QC: 2018-12-18
• Results First Posted: 2019-01-08
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-11
• Last Update Posted: 2019-03-11

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)

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

Saint Bernards Cancer Center; 🇺🇸 Jonesboro, Arkansas, United States

City of Hope; 🇺🇸 Duarte, California, United States

Compassionate Cancer Care Medical Group, Inc.; 🇺🇸 Fountain Valley, California, United States

Pacific Hematology Oncology Associates; 🇺🇸 San Francisco, California, United States

University of Colorado Health Memorial Hospital; 🇺🇸 Colorado Springs, Colorado, United States

Poudre Valley Hospital Harmony Campus; 🇺🇸 Fort Collins, Colorado, United States

Central Georgia Cancer Care; 🇺🇸 Macon, Georgia, United States

Loyola University Medical Center; 🇺🇸 Maywood, Illinois, United States

University of Iowa Hospitals and Clinics; 🇺🇸 Iowa City, Iowa, United States

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