A Randomized Phase IIb Placebo-Controlled Study of R-ICE Chemotherapy With and Without SGN-40 for Patients With DLBCL

Study Overview
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Brief Summary
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This is a randomized trial to estimate the activity of R-ICE plus SGN-40 vs. R-ICE plus placebo in patients with DLBCL. The study will assess safety and tolerability and will measure any additional clinical benefit observed in patients receiving SGN-40.

Official Title
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A Randomized Phase IIb Placebo-controlled Study of R-ICE Chemotherapy With and Without SGN-40 (Anti-CD40 Humanized Monoclonal Antibody) for Second-line Treatment of Patients With Diffuse Large B-Cell Lymphoma (DLBCL)

Conditions
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Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: SGN-40
* Drug: placebo
* Drug: rituximab
* Drug: etoposide
* Drug: carboplatin
* Drug: ifosfamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of de novo or transformed DLBCL, or follicular grade 3b lymphoma. Received at least four cycles of first-line therapy with R-CHOP, or equivalent. Best clinical response to first-line therapy of stable disease, partial response, or complete response. At least one measureable lesion that is both greater than or equal to 1.5cm by radiographic imaging and by positive FDG-PET scan. Exclusion Criteria: Leptomeningeal or central nervous system lymphoma. Received any therapy for relapsed or progressive disease except for local radiation, steroids, or rituximab. Received a hematopoietic stem cell transplant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>SGN-40, rituximab, etoposide, carboplatin, ifosfamide | Drug: SGN-40<br>* 2-8 mg/kg IV. Cycle 1: Days -1, 3, 8, 15; Cycles 2, 3: Days 1, 8, 15.<br>* Other names: dacetuzumab;Drug: rituximab<br>* 375 mg/m2 IV. Cycle 1: Day -2; Cycles 2, 3: Day 1<br>* Other names: Rituxan;Drug: etoposide<br>* 100 mg/m2 IV. Cycles 1-3: Days 1, 2 and 3.<br>* Other names: Toposar, Vepesid;Drug: carboplatin<br>* AUC=5 mg/mL min IV. Cycles 1-3: Day 2.<br>* Other names: Paraplatin;Drug: ifosfamide<br>* 5 g/m2 24 hr. IV infusion. Cycles 1-3: Day2.<br>* Other names: Ifex;|
| Placebo Comparator: 2<br>placebo, rituximab, etoposide, carboplatin, ifosfamide | Drug: placebo<br>* Volume as equivalent to corresponding SGN 40 dose IV. Cycle 1: Days -1, 3, 8, 15. Cycles 2, 3: Days 1, 8, 15.<br>Drug: rituximab<br>* 375 mg/m2 IV. Cycle 1: Day -2; Cycles 2, 3: Day 1<br>* Other names: Rituxan;Drug: etoposide<br>* 100 mg/m2 IV. Cycles 1-3: Days 1, 2 and 3.<br>* Other names: Toposar, Vepesid;Drug: carboplatin<br>* AUC=5 mg/mL min IV. Cycles 1-3: Day 2.<br>* Other names: Paraplatin;Drug: ifosfamide<br>* 5 g/m2 24 hr. IV infusion. Cycles 1-3: Day2.<br>* Other names: Ifex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response as assessed by CT and PET scans and revised response criteria for malignant lymphoma. |  | 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, laboratory values, and anti-drug antibody immune responses. |  | 9 weeks | 
| Partial response, failure free survival, overall survival, and response for one and two years following treatment. |  | Every 3 months for 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, Antigens, CD40, Hematologic Diseases, Immunoproliferative Disorders, Lymphatic Diseases, Antibody, Monoclonal, Combined Modality Therapy, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoproliferative Disorders