Non-Hodgkin Lymphoma, Mycosis Fungoides
Conditions
Keywords
non-Hodgkin, lymphoma, mycosis, fungoides
Brief summary
Brief summary TBD
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.
Interventions
DRUGCPG 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).
Sponsors
Lymphoma Research Foundation
American Society of Clinical Oncology
Ronald Levy
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. * Patients must have measurable disease other than the injection site or biopsy site. * 18 years of age or older * Karnofsky Performance Status (KPS) of \> 70. * Adequate bone marrow function: WBC\>4,000uL, hemoglobin \> 10g/dL; platelet count \>100,000/mm3; ANC\> 1000. * Adequate hepatic function: bilirubin \<= 1.5 mg/dL; SGOT/SGPT\<3xupper limit of normal * Adequate renal function: serum creatinine \<= 2.0mg/dL. * Required wash out periods for prior therapy: * Topical therapy: 2 weeks * Chemotherapy: 4 weeks * Radiotherapy (including photo therapy): 4 weeks * Systemic biological therapy for mycosis fungoides: 4 weeks * Other investigational therapy: 4weeks * 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 negative urine pregnancy test. * Life expectancy greater than 4 months. * 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. * 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. * Known history of human immunodeficiency virus (HIV), hepatitis B or hepatitis C (active, prior treatment, or both). * Patients with active infection or with a fever \>38.50 C within three days prior to the first scheduled treatment. * 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 CpG 7909 * Current anticoagulant therapy (ASA\<= 325mg/day allowed). * 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). * 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 |
|---|---|---|
| Objective Response Rate (ORR) | 12 weeks | Objective Response Rate (ORR) consisting of Complete Response (CR) + Partial Response (PR), not including Stable Disease (SD) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lymphoma, B-cell Low-grade (BCL) 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). | 15 |
| Mycosis Fungoides (MF) 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). | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Lymphoma, B-cell Low-grade (BCL) | Mycosis Fungoides (MF) | Total |
|---|---|---|---|
| Age, Continuous | 62 years | 57 years | 60 years |
| Sex: Female, Male Female | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 10 Participants | 12 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 15 | 15 / 15 |
| serious Total, serious adverse events | 0 / 15 | 1 / 15 |
Outcome results
Primary
Objective Response Rate (ORR)
Objective Response Rate (ORR) consisting of Complete Response (CR) + Partial Response (PR), not including Stable Disease (SD)
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lymphoma, B-cell Low-grade (BCL) | Objective Response Rate (ORR) | 26.7 percentage of treated subjects |
| Mycosis Fungoides (MF) | Objective Response Rate (ORR) | 35.7 percentage of treated subjects |