Clinical Trials /

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

NCT02927964

Description:

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.

Related Conditions:
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: TLR9 Agonist SD-101, Ibrutinib, and Radiation Therapy in Treating Patients With Relapsed or Refractory Grade 1-3A Follicular Lymphoma
  • Official Title: Intratumoral Injection of SD-101, an Immunostimulatory CpG, in Combination With Ibrutinib and Local Radiation in Relapsed or Refractory Low-Grade Follicular Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: IRB-36750
  • SECONDARY ID: NCI-2016-01065
  • SECONDARY ID: IRB-36750
  • SECONDARY ID: LYMNHL0135
  • SECONDARY ID: R35CA197353
  • NCT ID: NCT02927964

Conditions

  • Grade 1 Follicular Lymphoma
  • Grade 2 Follicular Lymphoma
  • Grade 3a Follicular Lymphoma
  • Recurrent Follicular Lymphoma
  • Refractory Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma

Interventions

DrugSynonymsArms
IbrutinibBTK Inhibitor PCI-32765, CRA-032765, PCI-32765Treatment (radiation therapy, TLR9 agonist SD-101, ibrutinib)
TLR9 Agonist SD-101ISS-ODN SD-101, SD-101Treatment (radiation therapy, TLR9 agonist SD-101, ibrutinib)

Purpose

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.

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
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (radiation therapy, TLR9 agonist SD-101, ibrutinib)ExperimentalPatients 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, and 30. Patients also receive ibrutinib PO daily beginning on day 9 for 96 weeks or in the absence of disease progression or unexpected toxicity.
  • Ibrutinib
  • TLR9 Agonist SD-101

Eligibility Criteria

        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.

          -  Subjects with active infection or with a fever > 38.50 C within 3 days prior to the
             first scheduled treatment.

          -  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, 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose-limiting toxicity assessed using Common Terminology Criteria for Adverse Events version 4.0 (Phase Ib)
Time Frame:Up to 60 months
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Progression-free survival (Phase II)
Time Frame:Up to 60 months
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Robert Lowsky

Last Updated

March 16, 2019