a safety study of sgn-40 in patients with non-hodgkin's lymphoma

Conditions: Non-Hodgkin Lymphoma

Summary: 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.

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.

Eligibility criteria:
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.

Keywords: antigens, cd40 antibody, monoclonal lymphoma, non-hodgkin lymphoma, b-cell hematologic diseases immunoproliferative disorders lymphatic diseases lymphoproliferative disorders lymphoma