Skip to main content

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

Trial Status: Active

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 grade 1-3a follicular 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.

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 >= 10 mm), percutaneously
  • Subjects 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 bone marrow involvement independent of transfusion support in either situation
  • Hemoglobin: >= 8 g/dL (may be transfused)
  • Creatinine clearance > 25 ml/min
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT): =< 3 x ULN
  • 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 [beta-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 including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren’s syndrome, autoimmune thrombocytopenia, history of 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 cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) 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 central nervous system (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, 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 (e.g., 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 (i.e. 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 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

California

Palo Alto
Stanford Cancer Institute Palo Alto
Status: ACTIVE
Contact: Ronald Levy
Phone: 650-725-6452

PRIMARY OBJECTIVES:

I. To determine the recommended phase 2 dose (RP2D) of intratumoral TLR9 agonist SD-101 (SD-101) in combination with ibrutinib and radiation in patients with relapsed or refractory B cell lymphoma. (Phase Ib)

II. To determine the safety and tolerability of SD-101 in combination with ibrutinib and radiation in patients with relapsed or refractory B cell lymphoma. (Phase Ib)

III. To evaluate the efficacy of intratumoral SD-101 in combination with ibrutinib and radiation in patients with relapsed or refractory low-grade B cell lymphoma by assessing overall response rate. (Phase II)

SECONDARY OBJECTIVES:

I. To evaluate progression-free survival after treatment with intratumoral SD-101 in combination with ibrutinib and radiation in patients with relapsed or refractory B-cell lymphoma. (Phase II)

II. 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. (Phase II)

OUTLINE: This is a phase Ib, dose-escalation study of TLR9 agonist SD-101 followed by a phase II study.

Patients undergo radiation therapy on days 1 and 2. Within 12 hours of the completion of radiation therapy, patients receive TLR9 agonist SD-101 intratumorally (IT) on days 2, 9, 16, 23, and 30. Patients also receive ibrutinib orally (PO) daily beginning on day 10 for 96 weeks in the absence of disease progression or unexpected toxicity.

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

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
Stanford Cancer Institute Palo Alto

Principal Investigator
Ronald Levy

  • Primary ID LYMNHL0135
  • Secondary IDs NCI-2016-01065
  • Clinicaltrials.gov ID NCT02927964