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

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

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

Study Overview

• Status: Completed
• Conditions: Lymphoma; Lymphoma, Non-Hodgkin; Lymphomas: Non-Hodgkin; Lymphomas: Non-Hodgkin Follicular / Indolent B-Cell
• Intervention / Treatment: Drug: PF-3512676; Radiation: Local radiotherapy

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PF-3512676; 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; 18 mg injection; Other Names: CpG 7909; CpG; ProMune; Radiation: Local radiotherapy; 2 gray (2 Gy) on each of Days 1 and 2

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ronald Levy
• Collaborators: Pfizer

Publications and helpful links

General Publications

• Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-Lopez A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. doi: 10.1200/JCO.1999.17.4.1244. Erratum In: J Clin Oncol 2000 Jun;18(11):2351.

Study record dates

Study Major Dates

• Study Start: January 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: April 10, 2009
• First Submitted That Met QC Criteria: April 13, 2009
• First Posted (Estimate): April 14, 2009

Study Record Updates

• Last Update Posted (Actual): March 14, 2017
• Last Update Submitted That Met QC Criteria: January 24, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: IRB-14820; SU-03272009-2038 (Other Identifier: SU IRB); LYMNHL0064 (Other Identifier: OnCore)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No