A Safety Study of SGN-40 in Patients With Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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This is an open-label, multi-dose, Phase I, dose escalation study to define the safety profile and preliminary anti-tumor activity of SGN-40 in patients with refractory or recurrent non-Hodgkin B-cell lymphomas.

Detailed Description
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A minimum of 3 patients will be entered into each dose-level cohort for 5 weeks. A dose-escalation schema will be employed in cohorts. The initial dose starts at 1 mg/kg on Day 1 and 4 followed by 2mg/kg on Day 8. Dose escalation will occur on weeks 3-5 with a maximum weekly dose of 8 mg/kg. Patients who meet criteria of at least partial response will be eligible for additional 4 weekly doses at highest dose tolerated.

Official Title
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A Phase I, Multi-Dose Study of SGN-40 (Anti-huCD40 mAb) in Patients With Non-Hodgkin's Lymphoma

Conditions
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Non-Hodgkin Lymphoma

Intervention / Treatment
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* Drug: SGN-40 (anti-huCD40 mAb)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have a histological diagnosis of B cell non-Hodgkin's lymphoma, including diffuse large B-cell, mantle cell, follicular, small lymphocytic, and marginal zone lymphoma by the World Health Organization criteria. Patients must have an archived paraffin or fresh tumor specimen available for immunohistologic evaluation of CD40, CD20, & CD79a. Patients must have relapsed lymphoma and must have failed frontline chemotherapy. Patients who have not received autologous stem cell transplant must have refused or be ineligible for it. Patients must have completed radiotherapy, chemotherapy, and/or treatment with investigational anti-cancer agents 4 weeks prior to registration. Patients must have completed any monoclonal antibody treatment, including rituximab, 6 months prior to registration. Patients must have completed autologous bone marrow transplant 4 months prior to registration. Patient must have at least one site of measurable disease defined by unidimensional lesion ≥ 2 cm by conventional CT scan. Patients must have an ECOG performance status ≤ 2 and a life expectancy > 3 months. Patients must have the following required baseline laboratory data: Platelet count ≥ 75,000/mm3, Hemoglobin ≥ 9.0 g/dL, Absolute neutrophil count ≥ 1,250/mm3, ALT/AST ≤ 2.5 times ULN, Total bilirubin ≤ 1.5 times ULN, Creatinine < 1.5 mg/dL, Females of childbearing potential must have a negative serum β-hCG pregnancy test result within 3 days prior to the first dose of SGN-40 and must agree to use an effective contraceptive method during the course of the study and for 6 months following the last dose of study drug. If a deep venous thrombosis or other vascular even has required medical or surgical intervention in the past year, patients must either be on stable dose of anticoagulant therapy for at least 3 weeks or have completed anticoagulant therapy at least 3 months prior to registration with radiographic confirmation that thrombosis is resolved. Patients must be at least 18 years of age. Patients must be available for periodic blood sampling, study-related assessments and management of toxicity at the treating institution. Exclusion Criteria: Patients with history or clinical evidence of leptomeningeal or central nervous system (CNS) lymphoma. Patients with a documented history within 6 months of registration of a cerebral vascular event, myocardial infarction, deep venous thrombosis or other vascular event that has required medical or surgical intervention. Patients must have completed anticoagulant therapy at least 3 months prior to registration. Prophylactic anticoagulant therapy for indwelling catheters is acceptable. Patients who have received an allogeneic stem cell transplant. Patients who have had major surgery within 4 weeks prior to registration. Patients with a known hypersensitivity to recombinant proteins or any excipient contained in the drug formulation. Patients with a history of another primary malignancy that has not been in remission for at least 5 years (non-melanoma skin cancer and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear are exempt from the five year limit). Patients with any active systemic viral, bacterial, or fungal infection within four weeks prior to registration. Patients with known positivity for HIV, hepatitis B or hepatitis C infection. Patients with a history of significant chronic or recurrent infections requiring treatment. Patients with a history of migraines or severe headaches requiring medical therapy within 12 months of enrollment. Patients on systemic steroids who have not been on a stable daily dose (not exceeding 10 mg prednisone or equivalent) during 4 weeks prior to the first dose of SGN 40. Patients who are pregnant or breastfeeding. Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment. Patients with dementia or altered mental status that would preclude the understanding and/or rendering of informed consent.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: SGN-40 (anti-huCD40 mAb)<br>* 1 mg/kg IV (in the vein) on Day 1; 1-2 mg/kg IV on Day 4; 2-4 mg/kg IV on Day 8; 3-8 mg/kg on Days 15, 22 and 29.<br>* Other names: dacetuzumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events and lab abnormalities. |  |  | 

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