A Phase II Study of Intratumoral Injection PF-3512676 in Combination With Local Radiation in Low-Grade B-Cell Lymphomas
1. Biopsy confirmed low-grade B-cell lymphoma, specifically,
follicular grade 1 or 2, marginal zone or small lymphocytic lymphoma, of any initial
stage. Patients may be either treatment-naïve or relapsed from or refractory to prior
therapy. Fifteen treatment-naïve and 15 relapsed/refractory patients will be enrolled.
2. Patients must have at least one site of disease that is accessible for intratumoral
injection of PF-3512676 percutaneously
3. Tumor specimens must be available for immunological studies either from a previous
biopsy or a new biopsy obtained before the initiation of the study.
4. Patients must have measurable disease other than the injection site or biopsy site.
5. ECOG Performance Status of 1 or better (corresponds to Karnofsky Performance Status
(KPS) of >= 70)
6. Patients must be 18 years of age or older.
7. Adequate bone marrow function: WBC >= 2,000/uL; platelet count >= 75,000/mm3; ANC>=
8. Adequate renal function: serum creatinine <= 2.0mg/dL.
9. Adequate hepatic function: bilirubin <=1.5 mg/dL; SGOT/SGPT < 3 x upper limit of
10.Required wash out periods for prior therapy:
1. Topical therapy: 2 weeks
2. Chemotherapy: 4 weeks
3. Radiotherapy: 4 weeks
4. Other investigational therapy: 4 weeks
5. Rituximab: 12 weeks
11.Patients of reproductive potential and their partners must agree to use an
effective (>90% reliability) form of contraception during the study and for 4 weeks
following the last study drug administration.
12.Women of reproductive potential must have negative urine pregnancy test. 13.Life
expectancy greater than 4 months. 14.Able to comply with the treatment schedule.
15.Ability to understand and the willingness to sign a written informed consent
Exclusion Criteria:A patient may not be enrolled in the trial if any of the following
criteria are met:
1. Pre-existing autoimmune or antibody mediated disease including: systemic lupus,
erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome,
autoimmune thrombocytopenia, but excluding controlled thyroid disease, or the
presence of autoantibodies without clinical autoimmune disease.
2. Known history of human immunodeficiency virus (HIV).
3. Patients with active infection or with a fever >38.50 C within three days prior
to the first scheduled treatment.
4. CNS metastases
5. Prior malignancy (active within 5 years of screening) except basal cell or
completely excised non-invasive squamous cell carcinoma of the skin, or in situ
squamous cell carcinoma of the cervix.
6. History of allergic reactions attributed to compounds of similar composition to
7. Current anticoagulant therapy (ASA <= 325 mg per day allowed).
8. Significant cardiovascular disease (i.e. NYHA class 3 congestive heart failure;
myocardial infarction with the past 6 months; unstable angina; coronary
angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac
9. Pregnant or lactating.
10. Any other medical history, including laboratory results, deemed by the
investigator to be likely to interfere with their participation in the study, or
to interfere with the interpretation of the results.
The principal investigator may grant a protocol exemption in cases where a patient
would be ineligible based on one or more exclusion criteria but would be a good
candidate for the study. In this case, a note to file must be generated to explain
the inclusion of the patient.