- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02254772
A Phase I/II Study of Intratumoral Injection of SD-101
A Phase I/II Study of Intratumoral Injection of SD-101, an Immunostimulatory CpG, and Intratumoral Injection of Ipilimumab, an Anti-CTLA4 Monoclonal Antibody, in Combination With Local Radiation in Low-Grade B-Cell Lymphomas
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Monoclonal antibodies, such as ipilimumab, may block cancer growth in different ways by targeting certain cells. Biological therapies, such as TLR9 agonist SD-101, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving ipilimumab in combination with TLR9 agonist SD-101 and radiation therapy may be a better treatment for B-cell lymphoma.
Study objectives are dose-limiting toxicity (DLT) and the treatment assessments tumor response and time-to-progression. Cohort 1 dose level is 10 mg ipilimumab, subsequent cohort is 5 or 25 mg ipilimumab.
- If 2 out of 6 patients experience a DLT in the first cohort (10 mg ipilimumab), the dose will be de-escalated to 5 mg ("Cohort -1").
- If 2 out of 6 patients experience a DLT at the 5 mg dose level, then the study will be stopped.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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California
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Stanford, California, United States, 94305
- Stanford University Hospitals and Clinics
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria
- Biopsy-confirmed low-grade B-cell lymphoma, specifically, follicular grade 1 or 2, or 3A marginal zone or small lymphocytic lymphoma; patients must have relapsed from or are refractory to prior therapy
- Patients must have at least one site of disease that is accessible for intratumoral injection of SD-101 and of ipilimumab (diameter ≥ 10mm), 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 of 0 or 1 [corresponds to Karnofsky Performance Status (KPS) of ≥ 70]
- White blood cell count (WBC) ≥ 2000/µL (2 x 10^9/L)
- Absolute neutrophil count (ANC) ≥ 1000/µL (0.5 x 10^9/L)
- Platelets ≥ 75 x 10^3/µL (75 x 10^9/L)
- Hemoglobin ≥ 8 g/dL (may be transfused)
- Creatinine ≤ 2.0 x upper limit of normal (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 x ULN for subjects without liver metastasis; ≤ 5 times for liver metastases
- Bilirubin ≤ 2.0 x ULN (except for subjects with Gilbert's Syndrome, who must have a total bilirubin of less than 3.0 mg/dL)
- No active or chronic infection with human immunodeficiency virus (HIV), Hepatitis B, or Hepatitis C
- Must be at least 4 weeks since treatment with standard or investigational chemotherapy, biochemotherapy, surgery, radiation, cytokine therapy, and 8 weeks since any monoclonal antibodies or immunotherapy, and recovered from any clinically significant toxicity experienced during treatment
- Patients of reproductive potential must agree to use an effective (> 90% reliability) form of contraception during the study and for 6 months 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
- 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, Addison's disease, but excluding the presence of auto-antibodies without clinical autoimmune disease
- History of inflammatory bowel disease (eg, Crohn's disease or ulcerative colitis), celiac disease, or other chronic gastrointestinal conditions associated with diarrhea, or current acute colitis of any origin
- Any history of diverticulitis, or evidence of diverticulitis at baseline, including evidence limited to computed tomography (CT) scan only (note diverticulosis is not an exclusion criterion)
- Severe psoriasis
- Active thyroiditis
- History of uveitis
- Known history of HIV; patients with Acquired Immunodeficiency Syndrome (AIDS) are excluded
- Patients with active infection or with a fever > 38.5 degrees C within 3 days prior to the first scheduled treatment
- Central nervous system (CNS) lymphoma
- 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 SD-101 or ipilimumab (anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA4] antibodies)
- Current anticoagulant therapy (EXCEPTION acetylsalicylic acid ≤ 325 mg per day allowed)
- Treatment with an immunosuppressive regimen of corticosteroids or other immunosuppressive medication (eg, methotrexate, rapamycin) within 30 days of study treatment; note patients with adrenal insufficiency may take up to 5 mg of prednisone or equivalent daily; topical and inhaled corticosteroids in standard doses are 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Treatment
Patients receive TLR9 agonist SD-101 via intratumoral injections; ipilimumab via intratumoral injection; and undergo radiation therapy on days 1 and 2.
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A dose of 10 mg in cohort 1 or 25mg in cohort 2 via intratumoral injection on day 2, week 1.
Other Names:
Started on day 2 week 1, then once every week x 4 successive weeks for a total of 5 injections.
Other Names:
Undergo low-dose radiation therapy to 1 site of disease
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Dose-limiting Toxicity (DLT) Events of Ipilimumab Plus a Fixed Dose of SD-101 (1 mg/Week)
Time Frame: Up to 10 weeks
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To determine the safety and tolerability of SD-101 (1 mg/week) and local low dose radiation plus escalating doses of subcutaneously (SC)-administered ipilimumab, the incidence of dose-limiting toxicities (DLT) will be assessed according to the following DLT definitions. Related adverse events (AEs) are toxicities. "Treatment" includes radiation therapy.
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Up to 10 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tumor Response
Time Frame: Up to 2 years
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Tumor response was assessed per the Cheson Criteria for low-grade B-cell lymphomas. Complete Response (CR) - No evidence disease. Partial Response (PR) - Regression of measurable disease with no new sites Progressive Disease (PD) - Any new lesion or increase by ≥ 50% of any previously-involved site after treatment nadir. Stable Disease (SD) - Any status that is not CR; PR; or PD. See references (Cheson BD, et al. J Clin Oncol. Apr 1999;17(4):1244. PubMed ID 10561185. |
Up to 2 years
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Median Time to Progression (TTP)
Time Frame: Up to 2 years
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Tumor progression was assessed as any new lesion or increase by ≥ 50% of any previously-involved site after treatment nadir.
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Up to 2 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Ronald Levy, MD, Stanford University Hospitals and Clinics
Publications and helpful links
General Publications
- Mooney KL, Czerwinski DK, Shree T, Frank MJ, Haebe S, Martin BA, Testa S, Levy R, Long SR. Serial FNA allows direct sampling of malignant and infiltrating immune cells in patients with B-cell lymphoma receiving immunotherapy. Cancer Cytopathol. 2022 Mar;130(3):231-237. doi: 10.1002/cncy.22531. Epub 2021 Nov 15.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Disease Attributes
- Leukemia, Lymphoid
- Leukemia
- Leukemia, B-Cell
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, B-Cell
- Recurrence
- Lymphoma, B-Cell, Marginal Zone
- Leukemia, Lymphocytic, Chronic, B-Cell
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Immune Checkpoint Inhibitors
- Ipilimumab
Other Study ID Numbers
- IRB-31133
- NCI-2014-01978 (REGISTRY: CTRP (Clinical Trial Reporting Program))
- LYMNHL0119 (OTHER: OnCore number)
- 5R01CA188005-02 (NIH)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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