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

Non-Hodgkin Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00103779
• Other study ID #: SG040-0002
• Status: Completed
• Phase: Phase 1
• First received: February 14, 2005
• Last updated: December 17, 2014
• Start date: December 2004
• Est. completion date: March 2007

Study information

• Verified date: December 2014
• Source: Seattle Genetics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: March 2007
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 ß-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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin Lymphoma

Intervention

Drug:
• SGN-40 (anti-huCD40 mAb)
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.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	University of Miami	Miami	Florida
United States	Cornell University	New York	New York
United States	Stanford University	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Seattle Genetics, Inc.	Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Advani R, Forero-Torres A, Furman RR, Rosenblatt JD, Younes A, Ren H, Harrop K, Whiting N, Drachman JG. Phase I study of the humanized anti-CD40 monoclonal antibody dacetuzumab in refractory or recurrent non-Hodgkin's lymphoma. J Clin Oncol. 2009 Sep 10;2 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events and lab abnormalities.			Yes

External Links

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