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

NCT ID: NCT02254772

Last Updated: 2019-11-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-09-30
• Study Completion Date: 2017-01-26

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.

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.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

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

Group Type: EXPERIMENTAL

Ipilimumab

Intervention Type: BIOLOGICAL

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

SD-101

Intervention Type: DRUG

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

Radiation therapy

Intervention Type: RADIATION

Undergo low-dose radiation therapy to 1 site of disease

Interventions

Ipilimumab

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

Intervention Type: BIOLOGICAL

SD-101

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

Intervention Type: DRUG

Radiation therapy

Undergo low-dose radiation therapy to 1 site of disease

Intervention Type: RADIATION

Other Intervention Names

Yervoy; MDX-010; MDX-CTLA-4; monoclonal antibody CTLA-4; ISS-ODN SD-101; TLR9 agonist; Irradiation; Radiotherapy

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Robert Lowsky

OTHER

Sponsor Role: lead

Responsible Party

Robert Lowsky

Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Ronald Levy, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University Hospitals and Clinics

Locations

Stanford University Hospitals and Clinics

Stanford, California, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 10561185 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34780125 (View on PubMed)

Other Identifiers

NCI-2014-01978

Identifier Type: REGISTRY

Identifier Source: secondary_id

LYMNHL0119

Identifier Type: OTHER

Identifier Source: secondary_id

5R01CA188005-02

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB-31133

Identifier Type: -

Identifier Source: org_study_id