A Phase I/II Study of Intratumoral Injection of SD-101
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|ClinicalTrials.gov Identifier: NCT02254772|
Recruitment Status : Completed
First Posted : October 2, 2014
Results First Posted : September 29, 2017
Last Update Posted : November 27, 2019
|Condition or disease||Intervention/treatment||Phase|
|Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Nodal Marginal Zone B-cell Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Small Lymphocytic Lymphoma Splenic Marginal Zone Lymphoma||Biological: Ipilimumab Drug: SD-101 Radiation: Radiation therapy||Phase 1 Phase 2|
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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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 Start Date :||September 2014|
|Actual Primary Completion Date :||November 10, 2016|
|Actual Study Completion Date :||January 26, 2017|
Patients receive TLR9 agonist SD-101 via intratumoral injections; ipilimumab via intratumoral injection; and undergo radiation therapy on days 1 and 2.
A dose of 10 mg in cohort 1 or 25mg in cohort 2 via intratumoral injection on day 2, week 1.
Started on day 2 week 1, then once every week x 4 successive weeks for a total of 5 injections.
Radiation: Radiation therapy
Undergo low-dose radiation therapy to 1 site of disease
- 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 ]
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.
- Grade 4 treatment-related AE
- Any drug-related AE ≥ Grade 3, including injection site reaction
- ≥ Grade 3 treatment-related clinical autoimmune reaction involving major organs (defined as liver, pancreas, lung, heart, kidney, bowel, bone marrow, eye, or central nervous system) which does not resolve to baseline or Grade 1 within 6 weeks
Treatment-related AE ≥ Grade 3 that persists despite adequate/maximal medical therapy and/or prophylaxis, EXCEPT
- Treatment-related skin rash ≤ Grade 3, that does not require systemic steroid therapy or other immunosuppressive therapy OR
- Grade 3 flu-like AEs
- Uveitis ≥ Grade 2
- Tumor Response [ Time Frame: Up to 2 years ]
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.
- Median Time to Progression (TTP) [ Time Frame: Up to 2 years ]Tumor progression was assessed as any new lesion or increase by ≥ 50% of any previously-involved site after treatment nadir.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02254772
|United States, California|
|Stanford University Hospitals and Clinics|
|Stanford, California, United States, 94305|
|Principal Investigator:||Ronald Levy, MD||Stanford University Hospitals and Clinics|