A Phase 1/2, Multi-Dose Study of SGN-40 (Anti-huCD40 mAb) in Patients With Chronic Lymphocytic Leukemia
1. Patients must have a histologic diagnosis of CLL as defined by the WHO criteria and
exhibit active disease requiring treatment as per the NCI working group on CLL.
2. Patients must have a fresh tumor specimen available (peripheral blood or bone marrow)
for flow cytometry evaluation (e.g. CD40, CD38, CD20, CD19, and CD5).For the phase 2
portion of the study, CD40 expression on malignant cells must be confirmed prior to
3. Patients must have relapsed after receiving at least one fludarabine containing
regimen or an equivalent purine analog.
At study start patients must be at least 8 weeks or 5 plasma half-lives (whichever is
greater) from prior chemotherapy/radiation/investigational agents, 8 weeks from prior
antibody therapy and 6 months from autologous stem cell transplant.
4. Patients must have an ECOG performance status ≤ 2 and a life expectancy > 3 months.
5. Patients must have the following required baseline laboratory data:
- Platelet count ≥ 50,000/mm3 (may be maintained by transfusion)
- Hemoglobin ≥ 7.5 g/dL (may be maintained by transfusions or growth factors)
- Absolute neutrophil count ≥ 1,000/mm3 (may be maintained by growth factors)
- ALT/AST ≤ 2.0 times ULN
- Total bilirubin ≤ 2.0 times ULN (unless related to hemolysis)
- Creatinine < 2.0 times ULN
6. Females of childbearing potential must have a negative B-hCG pregnancy test result
within 3 days prior to the first dose 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.
7. If a deep venous thrombosis or other vascular event has required medical or surgical
intervention in the past year, patients must either: a) be on a stable dose of
anticoagulant therapy (i.e., Coumadin and/or Heparin) for at least three weeks or b)
have completed anticoagulant therapy at least three months prior to registration with
radiographic confirmation that thrombosis is resolved. Prophylactic anticoagulant
therapy for indwelling catheters is acceptable.
8. Patients must be at least 18 years of age.
9. Patients must be available for periodic blood sampling, study-related assessments,
and management of toxicity at the treating institution.
10. Patients must give written informed consent. A copy of the signed informed consent
form will be retained by the treating institution.
1. Patients who have been treated previously with any anti-CD40 antibody.
2. Patients with a documented history within 6 months of registration of a cerebral
vascular event (stroke or TIA), unstable angina, or myocardial infarction.
3. Patients with active CNS or leptomeningeal disease.
4. Patients who have received allogeneic stem cell transplant.
5. Patients who have had major surgery within four weeks prior to enrollment.
6. Patients with a known hypersensitivity to recombinant proteins or any excipient
contained in the drug formulation.
7. 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
8. Patients with any systemic viral, bacterial, or fungal infection that has required
antibiotic therapy within four weeks prior to enrollment. Prophylactic antibiotics
and antiviral therapy are permitted prior to registration and are required during the
study period (e.g. Bactrim, acyclovir).
9. Patients with known HIV, hepatitis B (by surface antigen expression), or active
hepatitis C infection.
10. Patients on systemic steroids who have not been on a stable daily dose during the
four weeks immediately prior to first dose of SGN-40. Maximum steroid dose is 10 mg
prednisone per day or equivalent.
11. Patients with a history of migraines or severe headaches requiring medical therapy
(other than occasional acetaminophen, aspirin, or non-steroidal anti-inflammatory
drugs) within 12 months of enrollment.
12. Patients who are pregnant or breastfeeding.
13. Patients with any serious underlying medical condition that would impair their
ability to receive or tolerate the planned treatment.
14. Patients with dementia or altered mental status that would preclude the understanding
and/or rendering of informed consent.