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

• Sponsor: Ronald Levy (Other)
• Overall Status: Completed
• CT.gov ID: NCT00880581
• Collaborator: Pfizer (Industry)
• Enrollment: 30
• Location: 1
• Arm: 1
• Duration (Months): 72
• Patients Per Site Per Month: 0.4

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, Non-Hodgkin; Lymphoma; Lymphomas: Non-Hodgkin Follicular / Indolent B-Cell; Lymphomas: Non-Hodgkin	Drug: PF-3512676; Radiation: Local radiotherapy	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of Intratumoral Injection PF-3512676 in Combination With Local Radiation in Low-Grade B-Cell Lymphomas
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Jan 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Overall ObjectiveResponse (ORR) Rate [12 weeks]

   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

1. Response Rate After Cycle 2 [6 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Ronald Levy
• Pfizer

Investigators

• Principal Investigator: Ronald Levy, Stanford University

Study Documents (Full-Text)

None provided.

More Information

Publications

• Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López 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. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351.

• Responsible Party: Ronald Levy, Robert K. and Helen K. Summy Professor in the School of Medicine, Stanford University
• ClinicalTrials.gov Identifier: NCT00880581
• Other Study ID Numbers: IRB-14820; SU-03272009-2038; LYMNHL0064
• First Posted: Apr 14, 2009
• Last Update Posted: Mar 14, 2017
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin

Study Results

Participant Flow

Arm/Group Title	PF-3512676
Arm/Group Description	To assess the feasibility of using intra-tumoral PF-3512676 (CpG 7909 or ProMune) at 18 mg per week over 10 weeks in combination with local radiation [2 gray (2Gy) on each of Days 1 and 2] as a therapy for low-grade B-cell lymphoma.
Period Title: Cycle 1
STARTED	30
COMPLETED	30
NOT COMPLETED	0
Period Title: Cycle 1
STARTED	24
COMPLETED	24
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	PF-3512676
Arm/Group Description	To assess the feasibility of using intra-tumoral PF-3512676 in combination with local radiation as a therapy for lowgrade b-cell lymphoma.
Overall Participants	30
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	27 90%
>=65 years	3 10%
Sex: Female, Male (Count of Participants)
Female	15 50%
Male	15 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.7%
Not Hispanic or Latino	28 93.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.3%
White	26 86.7%
More than one race	0 0%
Unknown or Not Reported	3 10%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	PF-3512676
Arm/Group 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. PF-3512676: 18 mg injection Local radiotherapy: 2 x 2 Gy
Measure Participants	30
Complete Response (CR)	0 0%
Partial Response (PR)	7 23.3%
Stable Disease (SD)	19 63.3%
Progressive Disease (PD)	4 13.3%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants with progressive disease (PD) were not re-evaluated.

Arm/Group Title	PF-3512676
Arm/Group 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. PF-3512676: 18 mg injection Local radiotherapy: 2 x 2 Gy
Measure Participants	20
Complete Response (CR)	2 6.7%
Stable Disease (SD)	14 46.7%
Partial Response (PR)	4 13.3%

Adverse Events

Arm/Group Title	PF-3512676
Arm/Group 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.
All Cause Mortality
	PF-3512676
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	PF-3512676
	Affected / at Risk (%)	# Events
Total	0/30 (0%)
Other (Not Including Serious) Adverse Events
	PF-3512676
	Affected / at Risk (%)	# Events
Total	22/30 (73.3%)
General disorders
headache	6/30 (20%)	6
Musculoskeletal and connective tissue disorders
myalgia	11/30 (36.7%)	11
Skin and subcutaneous tissue disorders
erythema	17/30 (56.7%)	17

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.