Aflibercept and Standard Chemotherapy (R-CHOP) in First Line of Non Hodgkin B-cell Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to determine the selected dose of aflibercept when it is combined with R-CHOP treatment (Rituximab/Cyclophosphamide/Doxorubicin/Vincristine/Prednisone +/- intrathecal Methotrexate) administered every 2 weeks or every 3 weeks, in non Hodgkin B-cell lymphoma, and to determine how the body handles aflibercept when it is administered with R-CHOP.

Official Title
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A Phase I Open-label Dose-escalation Study of Intravenous Aflibercept (AVE0005, VEGF Trap) in Combination With R-CHOP Administered Every 2 Weeks or Every 3 Weeks in Patients With Non Hodgkin's B-cell Lymphoma

Conditions
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Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: aflibercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with non-Hodgkin B-cell lymphoma, good condition, not previously treated Exclusion Criteria: Contraindication to any drug contained in the R-CHOP (Rituximab/Cyclophosphamide/Doxorubicin/Vincristine/Prednisone +/- intrathecal Methotrexate) Less than 42 days elapsed from prior major surgery (28 days from other prior surgery) to the time of inclusion Cerebral or leptomeningeal involvement. History of another neoplasm (Adequately treated basal cell or squamous cell skin cancers, carcinoma in situ of the cervix, or any other cancer from which the patient has been disease free for > 5 years are allowed) Participation in another clinical trial and any concurrent treatment with any investigational drug within 30 days prior to the first drug intake Any acute or chronic medical condition, which could impair the ability of the patient to participate to the study or could interfere with interpretation of study results Uncontrolled diabetes mellitus Uncontrolled hypertension Abnormal kidney function Evidence of clinically significant bleeding diathesis, non-healing wound or underlying coagulopathy Pregnant or breast-feeding woman, or patient with reproductive potential (male, female) without an effective method of contraception History of hypersensitivity to any Trap agents or recombinant proteins

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aflibercept RCHOP 14<br>Aflibercept (25 mg/ml by IV over an hour) in combination with fixed dose of rituximab (R), cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) administered every 2 weeks. A dose of 2.0 mg/kg administered as Dose Level 1, 4.0 mg/kg as Dose Level 2, and 6.0 mg/kg dose as Dose level 3. | Drug: aflibercept<br>* in combination with standard treatment R-CHOP<br>|
| Experimental: Aflibercept RCHOP 21<br>Aflibercept (25 mg/ml by IV over an hour) in combination with fixed dose of rituximab (R), cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) administered every 3 weeks. A dose of 3.0 mg/kg administered as Dose Level 1, 6.0 mg/kg as Dose Level 2, and 8.0 mg/kg dose as Dose level 3. | Drug: aflibercept<br>* in combination with standard treatment R-CHOP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| selected dose of aflibercept based on Dose Limiting Toxicities observed |  | cycle 1 +/- 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events |  | treatment period | 
| Response rate |  | cycle 2, 4 and 8 | 
| Progression free survival |  | study period | 
| Biomarkers |  | Study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Hodgkin's lymphoma, angiogenesis inhibitors, CHOP protocol