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

NCT ID: NCT00103779

Last Updated: 2014-12-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-31
• Study Completion Date: 2007-03-31

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.

Conditions

Non-Hodgkin Lymphoma

Keywords

Antigens, CD40; Antibody, Monoclonal; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Hematologic Diseases; Immunoproliferative Disorders; Lymphatic Diseases; Lymphoproliferative Disorders; Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

SGN-40 (anti-huCD40 mAb)

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

dacetuzumab

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

Seagen Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Seattle Genetics, Inc.

Principal Investigators

Jonathan Drachman, MD

Role: STUDY_DIRECTOR

Seagen Inc.

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Stanford University

Stanford, California, United States

University of Miami

Miami, Florida, United States

Cornell University

New York, New York, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

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;27(26):4371-7. doi: 10.1200/JCO.2008.21.3017. Epub 2009 Jul 27.

Reference Type: RESULT

PMID: 19636010 (View on PubMed)

Related Links

http://www.ncbi.nlm.nih.gov/pubmed/19636010

Related Info

Other Identifiers

SG040-0002

Identifier Type: -

Identifier Source: org_study_id