A Phase II Intratumoral Injection PF-3512676 Plus Local Radiation in Low-Grade B-Cell Lymphomas

Lymphoma Clinical Trial

Official title:

A Phase II Study of Intratumoral Injection PF-3512676 in Combination With Local Radiation in Low-Grade B-Cell Lymphomas

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00880581
• Other study ID #: LYMNHL0064
• Secondary ID: SU-03272009-2038
• Status: Active, not recruiting
• Phase: Phase 2
• First received: April 10, 2009
• Last updated: December 30, 2012
• Start date: January 2009
• Est. completion date: September 2013

Study information

• Verified date: December 2012
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

To assess the feasibility of using intra-tumoral PF-3512676 in combination with local radiation as a therapy for lowgrade b-cell lymphoma.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: September 2013
• Est. primary completion date: September 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria: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>= 1000.

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 normal

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 document.

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 PF-3512676

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 arrhythmias).

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.

Study Design

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Lymphomas: Non-Hodgkin
• Lymphomas: Non-Hodgkin Follicular / Indolent B-Cell

Intervention

Drug:
• PF-3512676
18 mg injection

Radiation:
• Local radiotherapy
2 x 2 Gy

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Ronald Levy	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine local and systemic anti-tumor effects of intratumoral injection of CpG combined with local radiation in patients with low-grade B-cell lymphoma.		12 weeks after the initiation of therapy and q3monthly thereafter until progression.	No
Secondary	To determine the feasibility and safety of this treatment regimen.		12 weeks after the initiation of therapy and q3monthly thereafter until progression.	Yes
Secondary	To evaluate tumor-specific humoral and cellular immune responses.		12 weeks after the initiation of therapy and q3monthly thereafter until progression.	No