Lymphoma, Non-Hodgkin, Lymphoma, Lymphomas: Non-Hodgkin Follicular / Indolent B-Cell, Lymphomas: Non-Hodgkin
Conditions
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.
Interventions
DRUGPF-3512676
18 mg injection
RADIATIONLocal radiotherapy
2 gray (2 Gy) on each of Days 1 and 2
Sponsors
Pfizer
Ronald Levy
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-3512676 To assess the feasibility of using intra-tumoral PF-3512676 in combination with local radiation as a therapy for lowgrade b-cell lymphoma. | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | PF-3512676 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
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.
Time frame: 12 weeks
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-3512676 | Overall ObjectiveResponse (ORR) Rate | Complete Response (CR) | 0 participants |
| PF-3512676 | Overall ObjectiveResponse (ORR) Rate | Partial Response (PR) | 7 participants |
| PF-3512676 | Overall ObjectiveResponse (ORR) Rate | Stable Disease (SD) | 19 participants |
| PF-3512676 | Overall ObjectiveResponse (ORR) Rate | Progressive Disease (PD) | 4 participants |
Secondary
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.
Time frame: 6 months
Population: Participants with progressive disease (PD) were not re-evaluated.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PF-3512676 | Response Rate After Cycle 2 | Complete Response (CR) | 2 participants |
| PF-3512676 | Response Rate After Cycle 2 | Stable Disease (SD) | 14 participants |
| PF-3512676 | Response Rate After Cycle 2 | Partial Response (PR) | 4 participants |