Non-Hodgkin Lymphoma
Conditions
Keywords
Antigens, CD40, Antibody, Monoclonal, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell, Hematologic Diseases, Immunoproliferative Disorders, Lymphatic Diseases, Lymphoproliferative Disorders, Lymphoma
Brief 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.
Detailed description
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.
Interventions
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.
Sponsors
Genentech, Inc.
Seagen Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events and lab abnormalities. | — |
Countries
United States
Outcome results
None listed