CPG 7909 + Local Radiotherapy in Recurrent Low-Grade Lymphomas
Study Details
Study Description
Brief Summary
Brief summary TBD
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Detailed Description
This is a single institution phase 1-2 trial to evaluate the safety, feasibility and efficacy of CpG injections (4 intratumoral injections followed by 6 peri-tumoral injections) combined with local irradiation in patients with recurrent low-grade lymphomas.
Patients will receive low-dose radiotherapy to a single tumor site on days 1 and 2 (2 Gy each day). CpG injections will be administered into the same tumor site within the 24 hours before and the 24 hours after the radiation, and on days 8 and 15. Weekly doses of CpG will be then administered subcutaneously in the region of previous injections for 6 additional doses.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Lymphoma, B-cell low-grade (BCL) Recurrent low-grade B-cell lymphoma patients (at least one prior treatment failure) |
Drug: CPG 7909
6 mg intratumoral injection, administered immediately before 2 Gy radiotherapy (RT) to a designated tumor lesion, about 24 hours later after a 2nd 2 Gy RT dose, then weekly for 8 additional weeks (total of 10 injections).
Other Names:
|
| Experimental: Mycosis fungoides (MF) Mycosis fungoides patients must have failed or have been intolerant of at least 1 topical or 1 systemic treatment Recurrent mycosis fungoides patients (at least one prior failure of topical or systemic treatment) |
Drug: CPG 7909
6 mg intratumoral injection, administered immediately before 2 Gy radiotherapy (RT) to a designated tumor lesion, about 24 hours later after a 2nd 2 Gy RT dose, then weekly for 8 additional weeks (total of 10 injections).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Objective Response Rate (ORR) [12 weeks]
Objective Response Rate (ORR) consisting of Complete Response (CR) + Partial Response (PR), not including Stable Disease (SD)
Eligibility Criteria
Criteria
Inclusion Criteria:Patients must meet all of the following criteria in order to be eligible for entry into the trial.
-
Biopsy confirmed low-grade B-cell lymphoma of any initial stage or mycosis fungoides of stage IB-IVA. B-cell lymphoma patients must have failed at least one prior treatment. Mycosis fungoides patients must have failed or have been intolerant of at least 2 topical or one systemic treatment.
-
Patients must have at least one site of disease that is accessible for intratumoral injection of CpG percutaneously
-
Tumor specimens must be available for immunological studies either from a previous biopsy or a new biopsy obtained before the initiation of the treatment.
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Patients must have measurable disease other than the injection site or biopsy site.
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18 years of age or older
-
Karnofsky Performance Status (KPS) of > 70.
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Adequate bone marrow function: WBC>4,000uL, hemoglobin > 10g/dL; platelet count
100,000/mm3; ANC> 1000.
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Adequate hepatic function: bilirubin <= 1.5 mg/dL; SGOT/SGPT<3xupper limit of normal
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Adequate renal function: serum creatinine <= 2.0mg/dL.
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Required wash out periods for prior therapy:
-
Topical therapy: 2 weeks
-
Chemotherapy: 4 weeks
-
Radiotherapy (including photo therapy): 4 weeks
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Systemic biological therapy for mycosis fungoides: 4 weeks
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Other investigational therapy: 4weeks
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Rituximab: 12 weeks
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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.
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Women of reproductive potential must have negative urine pregnancy test.
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Life expectancy greater than 4 months.
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Able to comply with the treatment schedule.
Exclusion Criteria:A patient may not be enrolled in the trial if any of the following criteria are met.
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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, or the presence of autoantibodies without clinical autoimmune disease.
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Known history of human immunodeficiency virus (HIV), hepatitis B or hepatitis C (active, prior treatment, or both).
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Patients with active infection or with a fever >38.50 C within three days prior to the first scheduled treatment.
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CNS metastases
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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.
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History of allergic reactions attributed to compounds of similar composition to CpG 7909
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Current anticoagulant therapy (ASA<= 325mg/day allowed).
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Significant cardiovascular disease (i.e. 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).
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Pregnant or lactating.
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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
- Lymphoma Research Foundation
- American Society of Clinical Oncology
Investigators
- Principal Investigator: Ronald Levy, Stanford University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB-13063
- 80057
- LYMNHL0014
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Lymphoma, B-cell Low-grade (BCL) | Mycosis Fungoides (MF) |
|---|---|---|
| Arm/Group Description | Recurrent low-grade B-cell lymphoma patients (at least one prior treatment failure) CPG 7909: 6 mg intratumoral injection, administered immediately before 2 Gy radiotherapy (RT) to a designated tumor lesion, about 24 hours later after a 2nd 2 Gy RT dose, then weekly for 8 additional weeks (total of 10 injections). | Recurrent mycosis fungoides patients (at least one prior failure of topical or systemic treatment) CPG 7909: 6 mg intratumoral injection, administered immediately before 2 Gy radiotherapy (RT) to a designated tumor lesion, about 24 hours later after a 2nd 2 Gy RT dose, then weekly for 8 additional weeks (total of 10 injections). |
| Period Title: Overall Study | ||
| STARTED | 15 | 15 |
| COMPLETED | 15 | 14 |
| NOT COMPLETED | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | Lymphoma, B-cell Low-grade (BCL) | Mycosis Fungoides (MF) | Total |
|---|---|---|---|
| Arm/Group Description | Recurrent low-grade B-cell lymphoma patients (at least one prior treatment failure) CPG 7909: 6 mg intratumoral injection, administered immediately before 2 Gy radiotherapy (RT) to a designated tumor lesion, about 24 hours later after a 2nd 2 Gy RT dose, then weekly for 8 additional weeks (total of 10 injections). | Recurrent mycosis fungoides patients (at least one prior failure of topical or systemic treatment) CPG 7909: 6 mg intratumoral injection, administered immediately before 2 Gy radiotherapy (RT) to a designated tumor lesion, about 24 hours later after a 2nd 2 Gy RT dose, then weekly for 8 additional weeks (total of 10 injections). | Total of all reporting groups |
| Overall Participants | 15 | 15 | 30 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
62
|
57
|
60
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
5
33.3%
|
3
20%
|
8
26.7%
|
| Male |
10
66.7%
|
12
80%
|
22
73.3%
|
Outcome Measures
| Title | Objective Response Rate (ORR) |
|---|---|
| Description | Objective Response Rate (ORR) consisting of Complete Response (CR) + Partial Response (PR), not including Stable Disease (SD) |
| Time Frame | 12 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Lymphoma, B-cell Low-grade (BCL) | Mycosis Fungoides (MF) |
|---|---|---|
| Arm/Group Description | Recurrent low-grade B-cell lymphoma patients (at least one prior treatment failure) CPG 7909: 6 mg intratumoral injection, administered immediately before 2 Gy radiotherapy (RT) to a designated tumor lesion, about 24 hours later after a 2nd 2 Gy RT dose, then weekly for 8 additional weeks (total of 10 injections). | Recurrent mycosis fungoides patients (at least one prior failure of topical or systemic treatment) CPG 7909: 6 mg intratumoral injection, administered immediately before 2 Gy radiotherapy (RT) to a designated tumor lesion, about 24 hours later after a 2nd 2 Gy RT dose, then weekly for 8 additional weeks (total of 10 injections). |
| Measure Participants | 15 | 14 |
| Number [percentage of treated subjects] |
26.7
|
35.7
|
Adverse Events
| Time Frame | ||||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Lymphoma, B-cell Low-grade (BCL) | Mycosis Fungoides (MF) | ||
| Arm/Group Description | Recurrent low-grade B-cell lymphoma patients (at least one prior treatment failure) CPG 7909: 6 mg intratumoral injection, administered immediately before 2 Gy radiotherapy (RT) to a designated tumor lesion, about 24 hours later after a 2nd 2 Gy RT dose, then weekly for 8 additional weeks (total of 10 injections). | Recurrent mycosis fungoides patients (at least one prior failure of topical or systemic treatment) CPG 7909: 6 mg intratumoral injection, administered immediately before 2 Gy radiotherapy (RT) to a designated tumor lesion, about 24 hours later after a 2nd 2 Gy RT dose, then weekly for 8 additional weeks (total of 10 injections). | ||
All Cause Mortality |
||||
| Lymphoma, B-cell Low-grade (BCL) | Mycosis Fungoides (MF) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Lymphoma, B-cell Low-grade (BCL) | Mycosis Fungoides (MF) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/15 (0%) | 1/15 (6.7%) | ||
| General disorders | ||||
| Injection site reaction | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Lymphoma, B-cell Low-grade (BCL) | Mycosis Fungoides (MF) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/15 (33.3%) | 15/15 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Lymphadenopathy | 0/15 (0%) | 0 | 2/15 (13.3%) | 2 |
| Cardiac disorders | ||||
| Palpitation | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 |
| Gastrointestinal disorders | ||||
| Diarrhea | 0/15 (0%) | 0 | 4/15 (26.7%) | 4 |
| Nausea | 0/15 (0%) | 0 | 3/15 (20%) | 3 |
| Vomiting | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 |
| General disorders | ||||
| Flu like symptoms | 5/15 (33.3%) | 5 | 0/15 (0%) | 0 |
| Injection site reaction | 1/15 (6.7%) | 1 | 14/15 (93.3%) | 14 |
| Chills | 0/15 (0%) | 0 | 14/15 (93.3%) | 14 |
| Fatigue | 0/15 (0%) | 0 | 13/15 (86.7%) | 13 |
| Fever | 0/15 (0%) | 0 | 10/15 (66.7%) | 10 |
| Infections and infestations | ||||
| Rhinitis infective | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Myalgia | 0/15 (0%) | 0 | 10/15 (66.7%) | 10 |
| Arthralgia | 0/15 (0%) | 0 | 9/15 (60%) | 9 |
| Nervous system disorders | ||||
| Headache | 0/15 (0%) | 0 | 11/15 (73.3%) | 11 |
| Dizziness | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 0/15 (0%) | 0 | 2/15 (13.3%) | 2 |
| Skin and subcutaneous tissue disorders | ||||
| Hyperhidrosis | 0/15 (0%) | 0 | 1/15 (6.7%) | 1 |
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Ronald Levy, MD / Robert K and Helen K Summy Professor of Medicine |
|---|---|
| Organization | School of Medicine, Stanford University |
| Phone | 650-725-6452 |
| levy@stanford.edu |
- IRB-13063
- 80057
- LYMNHL0014