A Phase 2 Intratumoral Injection PF-3512676 Plus Local Radiation in Low-Grade B-Cell Lymphomas
Primary Purpose
Lymphoma, Non-Hodgkin, Lymphoma, Lymphomas: Non-Hodgkin Follicular / Indolent B-Cell
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PF-3512676
Local radiotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Non-Hodgkin
Eligibility Criteria
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.
Sites / Locations
- Stanford University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PF-3512676
Arm Description
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT00880581
First Posted
April 10, 2009
Last Updated
January 24, 2017
Sponsor
Ronald Levy
Collaborators
Pfizer
1. Study Identification
Unique Protocol Identification Number
NCT00880581
Brief Title
A Phase 2 Intratumoral Injection PF-3512676 Plus Local Radiation in Low-Grade B-Cell Lymphomas
Official Title
A Phase 2 Study of Intratumoral Injection PF-3512676 in Combination With Local Radiation in Low-Grade B-Cell Lymphomas
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
January 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Ronald Levy
Collaborators
Pfizer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
To assess the feasibility of using intra-tumoral PF-3512676 in combination with local radiation as a therapy for lowgrade b-cell lymphoma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Non-Hodgkin, Lymphoma, Lymphomas: Non-Hodgkin Follicular / Indolent B-Cell, Lymphomas: Non-Hodgkin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PF-3512676
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
PF-3512676
Other Intervention Name(s)
CpG 7909, CpG, ProMune
Intervention Description
18 mg injection
Intervention Type
Radiation
Intervention Name(s)
Local radiotherapy
Intervention Description
2 gray (2 Gy) on each of Days 1 and 2
Primary Outcome Measure Information:
Title
Overall ObjectiveResponse (ORR) Rate
Description
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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Response Rate After Cycle 2
Description
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.
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ronald Levy
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
10561185
Citation
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.
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A Phase 2 Intratumoral Injection PF-3512676 Plus Local Radiation in Low-Grade B-Cell Lymphomas
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