TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas

December 6, 2024 updated by: Ronald Levy

Intratumoral Injection of SD-101, an Immunostimulatory CpG, in Combination With BMS-986178 and Local Radiation in Low-Grade B-Cell Lymphomas

This phase I trial studies the side effects and best dose of the anti-OX40 antibody BMS-986178 when given together with the TLR9 agonist SD-101 and radiation therapy in treating patients with low-grade B-cell Non-Hodgkin lymphomas. TLR9 agonist SD-101 may stimulate the immune system in different ways and stop cancer cells from growing. Anti-OX40 antibody is a monoclonal antibody that enhances the activation of T cells, immune cells that are important for fighting tumors Radiation therapy uses high energy x-rays to kill cancer cells and may make them more easily detected by the immune system. Giving TLR9 agonist SD-101 together with anti-OX40 antibody BMS 986178 and radiation therapy may work better in treating patients with low-grade B-cell non-hodgkin lymphomas.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of TLR9 agonist SD-101 (SD-101) in combination with anti-OX40 antibody BMS 986178 (BMS-986178) and local low-dose radiation in patients with low-grade B-cell lymphoma. Adverse events and grades to be assessed by Common Terminology Criteria for Adverse Events (CTCAE) II. To determine the recommended phase 2 dose (RP2D) of BMS-986178 in combination with intratumoral SD-101 and radiation in patients with low-grade B-cell lymphoma.

SECONDARY OBJECTIVES:

I. To evaluate preliminary efficacy by assessing overall response rate and progression-free survival after treatment with intratumoral SD-101 in combination with BMS-986178 and radiation in patients with low-grade B-cell lymphoma.

OUTLINE: This is a phase I study of the combination of TLR9 agonist SD-101, anti-OX40 antibody BMS 986178, and local low-dose radiation therapy.

Patients receive radiation therapy on days 1-2, TLR9 agonist SD-101 intratumorally on days 2, 9, 16, 23, and 30, and anti-OX40 antibody BMS-986178 intravenously (IV) on days 3, 30, 58, 86, 114, and 142 in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-6 months for 72 weeks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
14

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Palo Alto, California, United States, 94304
        • Stanford University, School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Biopsy confirmed low-grade B-cell lymphoma, excluding gastric MALT lymphoma, high-risk mantle cell lymphoma, and currently transformed lymphoma
  • Patients must have at least one site of disease (cervical, axillary, inguinal, or subcutaneous) that is accessible for intratumoral injection of SD-101 (diameter ≥10mm) percutaneously and presents a low risk for complications from direct injections.
  • Patients must have at least one site of measurable disease, other than the injection site, which is not included in the radiation field
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Absolute neutrophil count (ANC) >= 1000/mm^3 independent of growth factor support
  • Platelets: >= 100,000/mm^3 or >= 50,000/mm^3 if known or suspected bone marrow involvement, independent of transfusion support in either situation
  • Hemoglobin: >= 8 g/dL (may be transfused)
  • Creatinine: Creatinine clearance > 25 ml/min
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT): =< 3 x upper limit of normal (ULN)
  • Bilirubin: =< 1.5 x ULN (except for subjects with Gilbert's Syndrome or of non-hepatic cause)
  • Must be at least 4 weeks since treatment with standard or investigational chemotherapy, biochemotherapy, surgery, radiation, cytokine therapy, any monoclonal antibodies or immunotherapy, and recovered from any clinically significant toxicity experienced during treatment
  • Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials; men must agree to not donate sperm during and after the study; for sexually active women of childbearing potential, these restrictions apply for 5 months after the last dose of study drug; for sexually active men, these restrictions apply for 7 months after the last dose of study drug
  • Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening, within 24 hours of the first dose of anti-OX40 antibody, and every four weeks while on study treatment; women who are pregnant or breastfeeding are ineligible for this study
  • Life expectancy greater than 3 months
  • Ability to comply with the treatment schedule
  • Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

  • Currently transformed lymphoma, high-risk mantle cell lymphoma, or gastric MALT lymphoma.
  • Need for immediate treatment or cytoreduction.
  • No easily accessible site for direct percutaneous injection with low-risk for potential complications.
  • Autoimmune disease requiring treatment within the last 5 years including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia, uveitis, or other if clinically significant
  • Major surgery within 4 weeks of enrollment, or a wound that has not fully healed
  • Vaccinated with live, attenuated vaccines within 4 weeks of enrollment
  • Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection
  • Known central nervous system (CNS) lymphoma
  • Patients with a history of prior malignancy with the exception of non-melanoma skin cancer, stage 1 prostate cancer that does not require treatment, or other malignancy that has undergone potentially curative therapy with no evidence of disease for the last 2 years and that is deemed by the investigators to be at low risk for recurrence. In situ cancer of any type and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is not an exclusion, though if surgery or other definitive intervention is planned, it should be completed prior to enrollment.
  • History of significant allergic reactions attributed to compounds of similar composition to SD-101 or BMS-986178
  • Treatment with an immunosuppressive regimen of corticosteroids or other immunosuppressive medication (e.g., methotrexate, rapamycin) within 30 days of study treatment; Note: patients may take up to 5 mg of prednisone or equivalent daily; topical and inhaled corticosteroids in standard doses are allowed
  • Significant cardiovascular disease (i.e. New York Heart Association [NYHA] class 3 congestive heart failure; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias)
  • Pregnant or breast feeding
  • Any other medical history, including laboratory results, deemed by the investigator likely to interfere with their participation in the study, or to interfere with the interpretation of the results

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Treatment (radiation therapy, SD-101, BMS-986178)
Patients receive radiation therapy on days 1-2, TLR9 agonist SD-101 and anti-OX40 antibody BMS-986178 intratumorally on days 2, 9, 16, 23, and 30, and anti-OX40 antibody BMS-986178 IV on days 2, 30, 58, 86, 114, and 142 in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studies
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Radiotherapeutics
  • RT
  • Therapy, Radiation
  • irradiation
  • radiotherapy
  • RADIATION
Biological: Anti-OX40 Antibody BMS 986178
Given IV, intratumoral
Other Names:
  • BMS 986178
  • BMS-986178
Drug: TLR9 Agonist SD-101
Given intratumorally
Other Names:
  • SD-101
  • ISS-ODN SD-101

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of participants experiencing Dose-limiting Toxicities (DLT) within 8 weeks of treatment initiation
Time Frame: Up to 8 weeks

Dose-limiting toxicities (DLTs) as assessed as the following hematologic toxicities (grades per CTCAE) in all participants receiving at least 1 intratumoral (IT) injection of SD-101 and at least 1 dose of BMS-986178 (not including events due to disease progression or definitively unrelated to study drugs):

  • Febrile neutropenia
  • Thrombocytopenia Grade 4 or Grade 3 with bleeding or platelet transfusion
  • Anemia Grade 4

  • Non-hematological toxicity ≥ grade 3, except:

    • Alopecia controlled by medical management
    • Nausea controlled by medical management
    • Grade 3 or 4 electrolyte abnormalities not associated with adverse events, persist < 72 hours, and either spontaneously resolve or respond to intervention.
    • Grade 3 or 4 elevation of amylase or lipase not associated with pancreatitis
    • Grade 3 endocrinopathy
    • Grade 3 infusion reaction returning to ≤ Grade 1 in < 6 hours
    • Grade 3 skin rash not requiring systemic steroid or other immunosuppressive therapy
Up to 8 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: Up to 96 weeks

Overall Response Rate (ORR), assessed as the sum of the complete response (CR) and partial response (PR) rates, as determined by computed tomography (CT) or positron emission tomography (PET)/CT and evaluated per the Lugano classification for low-grade B-cell lymphomas, in all participants receiving at least 1 intratumoral (IT) injection of SD-101 and at least 1 dose of BMS-986178.

Lugano classification:

  • CR: No detectable disease by CT or PET/CT scan
  • PR: ≥ 50% decrease in size of target lesions
  • No response (NR) / Stable disease (SD): < 50% decrease in size of target lesions
  • Progressive disease (PD): Target lesions larger; clear progression of non-target lesions; or new tumor lesions; new or recurrent bone marrow involvement; splenomegaly + 2 cm or +50%.

Reported for 24, 48, 72 and 96 weeks.
Up to 96 weeks
Progression-Free Survival (PFS)
Time Frame: up to 96 weeks

Progression-free survival (PFS) as determined for all participants receiving at least 1 intratumoral (IT) injection of SD-101 and at least 1 dose of BMS-986178, from start of treatment to disease progression per the Lugano classification or death from any cause, through 96 weeks. Progression assessed per the Lugano classification. Patients who were last known to be alive and progression-free will be censored at the latest disease assessment.

Lugano classification:

  • CR: No detectable disease by CT or PET/CT scan
  • PR: ≥ 50% decrease in size of target lesions
  • No response (NR) / Stable disease (SD): < 50% decrease in size of target lesions
  • Progressive disease (PD): Target lesions larger; clear progression of non-target lesions; or new tumor lesions; new or recurrent bone marrow involvement; splenomegaly + 2 cm or +50%.

Reported for 24, 48, 72 and 96 weeks.
up to 96 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ronald Levy

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ronald Levy, Stanford University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 9, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 9, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 10, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 19, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 19, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 25, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 11, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 6, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB-44250
  • NCI-2017-02452 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • LYMNHL0144 (Other Identifier: OnCore)
  • R35CA197353 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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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