A Phase 2 Intratumoral Injection PF-3512676 Plus Local Radiation in Low-Grade B-Cell Lymphomas

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

Official Title
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A Phase 2 Study of Intratumoral Injection PF-3512676 in Combination With Local Radiation in Low-Grade B-Cell Lymphomas

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

Intervention / Treatment
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* Drug: PF-3512676
* Radiation: Local radiotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy confirmed low-grade B-cell lymphoma diagnosed as follicular grade 1 or 2, marginal zone or small lymphocytic lymphoma of any initial stage. Patients may be either treatment-naïve; relapsed from; or refractory to prior therapy. (15 treatment-naïve and 15 relapsed/refractory patients will be enrolled) Patients must have at least one site of disease that is accessible for intratumoral injection of PF-3512676 percutaneously Tumor specimens must be available for immunological studies either from a previous biopsy or a new biopsy obtained before the initiation of the study. Patients must have measurable disease other than the injection site or biopsy site. Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 1 Karnofsky Performance Status (KPS) of ≥ 70 ≥ 18 years of age White blood cells (WBC) ≥ 2,000/uL Platelet count ≥ 75,000/mm³ Absolute neutrophil count (ANC) ≥ 1000 Serum creatinine ≤ 2.0 mg/dL. Bilirubin ≤ 1.5 mg/dL Serum glutamic oxalocetic transaminase (SGOT) / serum glutamic pyruvic transaminase (SGPT) ratio < 3 x upper limit of normal (ULN) Required wash out periods for prior therapy: Topical therapy: 2 weeks Chemotherapy: 4 weeks Radiotherapy: 4 weeks Other investigational therapy: 4 weeks Rituximab: 12 weeks 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. Women of reproductive potential must have a negative urine pregnancy test. Life expectancy > 4 months. Able to comply with the treatment schedule. Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: 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 Presence of autoantibodies without clinical autoimmune disease. Known history of human immunodeficiency virus (HIV). Patients with active infection or with a fever > 38.5 C within 3 days prior to the first scheduled treatment. Central nervous system (CNS) metastases 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. History of allergic reactions attributed to compounds of similar composition to PF-3512676 Current anticoagulant therapy [aspirin (ASA) ≤ 325 mg per day allowed] Significant cardiovascular disease [ie, New York Heart Association (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]. Pregnant or lactating. 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PF-3512676<br>Patients will be treated with 18 mg PF-3512676 by intratumoral injection on day 2 following local radiotherapy, then weekly for a total of 10 injections over 10 weeks. | Drug: PF-3512676<br>* 18 mg injection<br>* Other names: ProMune;Radiation: Local radiotherapy<br>* 2 gray (2 Gy) on each of Days 1 and 2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall ObjectiveResponse (ORR) Rate | Overall objective response rate (OOR) at time of best response was assessed as the sum of the Complete Response (CR) rate and the Partial Response (CR, PR) rate. Response was assessed per the Cheson Criteria, as below. Complete Response (CR) = Complete disappearance of all lesions, evidence, and effects of disease CR/unconfirmed (CRu) = residual lymph node mass >1.5 cm but regressed >75%, with 1 residual lymph node mass >1.5 cm that has regressed by >75% and/or increased number or size of bone marrow aggregates without cytologic or architectural atypia Partial Response (PR) = ≥50% decrease in SPD of the 6 largest lesions with no increase in the size of the other nodes; splenic / hepatic nodules regress ≥50%, and with no new sites of disease Stable disease (SD) = less than PR. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate After Cycle 2 | Response after a second cycle of treatment was assessed per the Cheson Criteria, as below. Complete Response (CR) = Complete disappearance of all lesions, evidence, and effects of disease CR/unconfirmed (CRu) = residual lymph node mass >1.5 cm but regressed >75%, with 1 residual lymph node mass >1.5 cm that has regressed by >75% and/or increased number or size of bone marrow aggregates without cytologic or architectural atypia Partial Response (PR) = ≥50% decrease in SPD of the 6 largest lesions with no increase in the size of the other nodes; splenic / hepatic nodules regress ≥50%, and with no new sites of disease Stable disease (SD) = less than PR. | 6 months |