A Phase I/II Study of Intratumoral Injection of SD-101

NCT02254772 | Completed Phase 1 Results DMC FDA Drug

• 4 other identifiers: IRB-31133NCI-2014-01978LYMNHL01195R01CA188005-02
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 1-2 trial studies the side effects and best dose of ipilimumab in combination with toll-like receptor 9 (TLR9) agonist SD-101 and radiation therapy in treating patients with recurrent low-grade B-cell lymphoma.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Number of Dose-limiting Toxicity (DLT) Events of Ipilimumab Plus a Fixed Dose of SD-101 (1 mg/Week)

  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

  Up to 10 weeks

Secondary Outcomes (2)

• Tumor Response

  Up to 2 years

• Median Time to Progression (TTP)

  Up to 2 years

Study Arms (1)

Treatment

EXPERIMENTAL

Patients receive TLR9 agonist SD-101 via intratumoral injections; ipilimumab via intratumoral injection; and undergo radiation therapy on days 1 and 2.

Biological: Ipilimumab; Drug: SD-101; Radiation: Radiation therapy

Interventions

Ipilimumab BIOLOGICAL

A dose of 10 mg in cohort 1 or 25mg in cohort 2 via intratumoral injection on day 2, week 1.

Also known as: Yervoy, MDX-010, MDX-CTLA-4, monoclonal antibody CTLA-4

Treatment

SD-101 DRUG

Started on day 2 week 1, then once every week x 4 successive weeks for a total of 5 injections.

Also known as: ISS-ODN SD-101, TLR9 agonist

Treatment

Radiation therapy RADIATION

Undergo low-dose radiation therapy to 1 site of disease

Also known as: Irradiation, Radiotherapy

Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Robert Lowsky: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Stanford University Hospitals and Clinics

Stanford, California, 94305, United States

Location

Related Publications (2)

• 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.

  PMID: 10561185 BACKGROUND

• 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.

  PMID: 34780125 DERIVED

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular; Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

Ipilimumab; CTLA-4 Antigen; Radiotherapy; Radiation

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Therapeutics; Physical Phenomena

Results Point of Contact

• Title: Ronald Levy, MD, Professor of Medicine
• Organization: Stanford Univeristy Medical Center

levy@stanford.edu

650-725-6452

Study Officials

• Ronald Levy, MD

  Stanford University Hospitals and Clinics

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: September 29, 2014
• First Posted: October 2, 2014
• Study Start: September 1, 2014
• Primary Completion: November 10, 2016
• Study Completion: January 26, 2017
• Last Updated: November 27, 2019
• Results First Posted: September 29, 2017

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)