TLR9 Agonist SD-101, Ibrutinib, and Radiation Therapy in Treating Patients With Relapsed or Refractory Grade 1-3A Follicular Lymphoma

November 20, 2023 updated by: Robert Lowsky

Intratumoral Injection of SD-101, an Immunostimulatory CpG, in Combination With Ibrutinib and Local Radiation in Relapsed or Refractory Low-Grade Follicular Lymphoma

This phase Ib/II trial studies the side effects and best dose of toll-like receptor 9 (TLR9) agonist SD-101 when given together with ibrutinib and radiation therapy and to see how well they work in treating patients with Low Grade Follicular Lymphoma, Marginal Zone Lymphoma, or Mantle Cell Lymphoma that has come back after a period of improvement or no longer responds to treatment. Immunostimulants such as TLR9 agonist SD-101 may increase the ability of the immune system to fight infection and disease. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving TLR9 agonist SD-101 with ibrutinib and radiation therapy may induce an immune response and prolong anti-tumor response.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Primary Objective:

Phase 1b: - To determine the recommended phase 2 dose (RP2D) of intratumoral SD 101 in combination with ibrutinib and radiation in subjects with relapsed or refractory B cell lymphoma . - To determine the safety and tolerability of SD 101 in combination with ibrutinib and radiation in subjects with relapsed or refractory B cell lymphoma

Phase 2: -To evaluate the efficacy of intratumoral SD 101 in combination with ibrutinib and radiation in subjects with relapsed or refractory B cell lymphoma by assessing overall response rate

Secondary Objective:

Phase 2: - To evaluate progression free survival after treatment with intratumoral SD 101 in combination with ibrutinib and radiation in subjects with relapsed or refractory B cell lymphoma

- To evaluate the induction of tumor-specific immune responses by treatment with intratumoral SD-101 in combination with ibrutinib and radiation in patients with relapsed or refractory B cell lymphoma

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2
  • 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

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • Biopsy confirmed Grade 1 or 2, or 3A follicular lymphoma; mantle cell lymphoma; or marginal zone lymphoma. Subjects must have relapsed from or are refractory to prior therapy.
  • Subjects must have at least one site of disease that is accessible for intratumoral injection of SD 101 (diameter ≥ 10mm), percutaneously.
  • Subjects must have at least one site of measurable disease (see Section 10.2.2 for definition of measurable disease) other than the injection site which is not included in the radiation field.
  • ECOG Performance Status of 0 or 1
  • Subjects must be 18 years of age or older.

  • Required values for initial laboratory tests:

    1. Absolute neutrophil count (ANC) ≥ 1000/mm3 independent of growth factor support
    2. Platelets: ≥ 100,000/mm3 or ≥ 50,000/mm3 if bone marrow involvement independent of transfusion support in either situation
    3. Hemoglobin: ≥ 8 g/dL (may be transfused)
    4. Creatinine: Creatinine clearance > 25 mL/min
    5. AST/ALT: ≤ 3 x ULN
    6. Bilirubin: ≤ 1.5 x ULN (except for subjects with Gilbert's Syndrome or of non hepatic origin)
  • 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.
  • 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 females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug.
  • Women of childbearing potential must have a negative serum (beta human chorionic gonadotropin [β-hCG]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study.
  • 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

  • Autoimmune disease requiring treatment within the last 5 years including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjӧgren's syndrome, autoimmune thrombocytopenia, uveitis, or other if clinically significant
  • Major surgery or a wound that has not fully healed within 4 weeks of enrollment.
  • History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists.
  • Requires chronic treatment with strong CYP3A inhibitors.
  • 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 CNS lymphoma.
  • Subjects with a history of prior malignancy with the exception of non melanoma skin cancer, carcinoma in situ of the cervix, in situ carcinoma of the bladder, 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 investigator to be a low risk for recurrence.
  • History of allergic reactions attributed to compounds of similar composition to SD 101 or ibrutinib
  • Treatment with an immunosuppressive regimen of corticosteroids or other immunosuppressive medication (eg, methotrexate, rapamycin) within 30 days of study treatment. Note: subjects may take up to 5 mg of prednisone or equivalent daily. Topical and inhaled corticosteroids in standard doses are allowed.
  • Significant cardiovascular disease (ie, 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 breast feeding.
  • 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

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
Intervention / Treatment
Experimental: Treatment (radiation therapy, TLR9 agonist SD-101, ibrutinib)
Patients undergo radiation therapy on days 1 and 2. Within 12 hours of the completion of radiation therapy, patients receive TLR9 agonist SD-101 IT on day 2 and on days 9, 16, 23, 30 and 37. Patients also receive ibrutinib PO daily beginning on day 9 for 96 weeks or in the absence of disease progression or unexpected toxicity.
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
  • RADIATION
Drug: Ibrutinib
Given PO
Other Names:
  • PCI-32765
  • BTK Inhibitor PCI-32765
  • CRA-032765
Drug: TLR9 Agonist SD-101
Given IT
Other Names:
  • SD-101
  • ISS-ODN SD-101

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of dose-limiting toxicity assessed using Common Terminology Criteria for Adverse Events version 4.0 (Phase Ib)
Time Frame: Up to 60 months
Dose-limiting toxicity will be assessed continuously throughout the trial. Adverse event information will be collected at each visit. Safety labs will be collected on week 2, 4, 6, 12 and every 12 weeks thereafter until the final study visit.
Up to 60 months
Tumor response rates (Phase II)
Time Frame: Up to 60 months
Tumor response rate of intratumoral SD 101 in combination with ibrutinib and radiation in subjects will be assessed. Tumor response rates (complete response, partial response) will be calculated based on the Lugano classification for low-grade B-cell lymphomas.
Up to 60 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (Phase II)
Time Frame: Up to 60 months
Progression free Survival is defined as the time elapsed between treatment initiation (Day 1) and tumor progression or death from any cause. Progression will be defined using the Lugano Classification. This outcome will be measured on any individual who has received at least one intratumoral injection of SD 101 at the recommended phase 2 dose level.
Up to 60 months

Collaborators and Investigators

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

Sponsor

Robert Lowsky

Collaborators

National Cancer Institute (NCI)
Janssen, LP
The Leukemia and Lymphoma Society
Rising Tide Foundation

Investigators

  • Principal Investigator: Michael Khodadoust, Stanford University
  • 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)

November 7, 2016

Primary Completion (Actual)

May 18, 2023

Study Completion (Actual)

May 18, 2023

Study Registration Dates

First Submitted

October 6, 2016

First Submitted That Met QC Criteria

October 6, 2016

First Posted (Estimated)

October 7, 2016

Study Record Updates

Last Update Posted (Actual)

November 22, 2023

Last Update Submitted That Met QC Criteria

November 20, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-36750 (Other Identifier: Stanford IRB)
  • R35CA197353 (U.S. NIH Grant/Contract)
  • NCI-2016-01065 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • LYMNHL0135 (Other Identifier: OnCore)

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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