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

Study Overview
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Brief Summary
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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
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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).

Official Title
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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

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

Intervention / Treatment
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* Drug: denintuzumab mafodotin
* Drug: rituximab
* Drug: cyclophosphamide
* Drug: doxorubicin
* Drug: vincristine
* Drug: prednisone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SGN-19A, DLBCL, Follicular Lymphoma Grade 3b, immunosuppressive agents, Antibodies, Monoclonal, Denintuzumab Mafodotin, Antibody-Drug Conjugate, Antigens, CD19, Hematologic Diseases, Immune System Diseases, Immunoproliferative Disorders, Immunotherapy, Lymphatic Diseases, Lymphoma, Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Monomethyl auristatin F, Neoplasms, Neoplasms by Histologic Type, Transformed Lymphoma / DLBCL, Cyclophosphamide, Doxorubicin, Liposomal doxorubicin, Prednisone, Rituximab, Vincristine, Alkylating Agents, Anti-Inflammatory Agents, Antibiotic, Antineoplastic, Antimitotic Agents, Antineoplastic Agents, Alkylating, Antineoplastic Agents, Phytogenic Antirheumatic Agents, Glucocorticoids, Drug Therapy