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

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by Robert Lowsky, Stanford University
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Robert Lowsky, Stanford University
ClinicalTrials.gov Identifier:
NCT02927964
First received: October 6, 2016
Last updated: April 6, 2017
Last verified: April 2017
  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 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.

Condition Intervention Phase
Grade 1 Follicular Lymphoma Grade 2 Follicular Lymphoma Grade 3a Follicular Lymphoma Recurrent Follicular Lymphoma Refractory Follicular Lymphoma Drug: Ibrutinib Other: Laboratory Biomarker Analysis Radiation: Radiation Therapy Drug: TLR9 Agonist SD-101 Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Robert Lowsky, Stanford University:

Primary Outcome Measures:
  • 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.

  • Tumor response rates (Phase II) [ Time Frame: Up to 60 months ]
    Tumor response rates (complete response, partial response) will be calculated based on the Lugano classification for low-grade B-cell lymphomas.


Secondary Outcome Measures:
  • Progression-free survival (Phase II) [ Time Frame: Up to 60 months ]
    Progression will be defined using the Lugano Classification.


Estimated Enrollment: 30
Study Start Date: November 2016
Estimated Study Completion Date: November 2021
Estimated Primary Completion Date: November 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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, and 30. Patients also receive ibrutinib PO daily beginning on day 10 for 96 weeks or in the absence of disease progression or unexpected toxicity.
Drug: Ibrutinib
Given PO
Other Names:
  • BTK Inhibitor PCI-32765
  • CRA-032765
  • PCI-32765
Other: Laboratory Biomarker Analysis
Correlatives studies
Radiation: Radiation Therapy
Undergo radiation therapy
Other Names:
  • Cancer Radiotherapy
  • Irradiate
  • Irradiated
  • Irradiation
  • RADIATION
  • Radiotherapeutics
  • Radiotherapy
  • RT
  • Therapy, Radiation
Drug: TLR9 Agonist SD-101
Given IT
Other Names:
  • ISS-ODN SD-101
  • SD-101

Detailed Description:

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 low-grade follicular 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 low-grade follicular 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 follicular 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 low-grade follicular 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 day 2 and on days 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Biopsy confirmed grade 1 or 2, or 3A follicular 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 (diameter >= 10 mm), 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 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
  • Patients with active infection or with a fever > 38.50 degrees Celsius (C) within three days prior to the first scheduled treatment
  • Known central nervous system (CNS) lymphoma
  • Patients 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 diagnosed > 5 years ago that has undergone potentially curative therapy with no evidence of disease for the last > 5 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: 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 (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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02927964

Contacts
Contact: Destiny Phillips 650-498-1313 destinyp@stanford.edu
Contact: Hollis Moore 650-725-8589 hollis.moore@stanford.edu

Locations
United States, California
Stanford University, School of Medicine Recruiting
Palo Alto, California, United States, 94304
Contact: Destiny Phillips    650-498-1313    destinyp@stanford.edu   
Contact: Hollis Moore    650-725-8589    hollis.moore@stanford.edu   
Principal Investigator: Ronald Levy         
Principal Investigator: Michael Khodaoust         
Sponsors and Collaborators
Robert Lowsky
National Cancer Institute (NCI)
Investigators
Principal Investigator: Ronald Levy Stanford University
Principal Investigator: Michael Khodadoust Stanford University
  More Information

Responsible Party: Robert Lowsky, Professor of Medicine, Stanford University
ClinicalTrials.gov Identifier: NCT02927964     History of Changes
Other Study ID Numbers: LYMNHL0135
NCI-2016-01065 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
36750 ( Other Identifier: Stanford IRB )
P30CA124435 ( US NIH Grant/Contract Award Number )
Study First Received: October 6, 2016
Last Updated: April 6, 2017

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin

ClinicalTrials.gov processed this record on June 23, 2017