Grade 1 Follicular LymphomaPhase 1/2NCT02927964
TLR9 Agonist SD-101, Ibrutinib, and Radiation Therapy in Treating Patients With Relapsed or Refractory Grade 1-3A Follicular Lymphoma
A Phase 1/2 study testing Ibrutinib, Radiation Therapy and TLR9 Agonist SD-101 in people with Grade 1 Follicular Lymphoma and Grade 2 Follicular Lymphoma, run by Robert Lowsky at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Grade 1 Follicular Lymphoma, Grade 2 Follicular Lymphoma, Grade 3a Follicular Lymphoma
- What is being tested?
- Ibrutinib, Radiation Therapy and TLR9 Agonist SD-101
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Nov 2016to 18 May 2023
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- Absolute neutrophil count (ANC) ≥ 1000/mm3 independent of growth factor support
- Platelets: ≥ 100,000/mm3 or ≥ 50,000/mm3 if bone marrow involvement independent of transfusion support in either situation
- Hemoglobin: ≥ 8 g/dL (may be transfused)
- Creatinine: Creatinine clearance > 25 mL/min
- AST/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 [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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University, School of Medicine
Palo Alto, California, 94304
About this study
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
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.
Read the 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
- Conditions
- Grade 1 Follicular Lymphoma, Grade 2 Follicular Lymphoma, Grade 3a Follicular Lymphoma, Recurrent Follicular Lymphoma, Refractory Follicular Lymphoma, Mantle Cell Lymphoma
- Being tested
- Ibrutinib, Radiation Therapy, TLR9 Agonist SD-101
- Medical subject headings
- Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IbrutinibDrug
Also called BTK Inhibitor PCI-32765, CRA-032765, PCI-32765
Given PO
Radiation TherapyRadiation
Also called Cancer Radiotherapy, Irradiate, Irradiated, Irradiation
Undergo radiation therapy
TLR9 Agonist SD-101Drug
Also called ISS-ODN SD-101, SD-101
Given IT
| Study group | Role | What they receive |
|---|---|---|
| Phase 1b -SD-101 3mg | Experimental | 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. Receives: Drug: Ibrutinib; Radiation: Radiation Therapy; Drug: TLR9 Agonist SD-101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Dose-limiting Toxicity Assessed Using Common Terminology Criteria for Adverse Events Version 4.0 (Phase Ib)
Dose-limiting toxicity was continuously throughout the trial. Adverse event information was collected at each visit. Safety labs were collected on week 2, 4, 6, 12 and every 12 weeks thereafter until the final study visit.
Measured: Up to 24 months
Tumor Response Rates (Phase II)
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.
Measured: Up to 24 months
Secondary outcomes (1)
Progression-free Survival (Phase II)
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.
Measured: Up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2016 (estimated)
- Study start7 Nov 2016
- Primary completion18 May 2023
- Study completion18 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Grade 1 Follicular LymphomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Robert Lowsky
- Sponsor type
- University, hospital or other
- Collaborators
- Janssen, LP, National Cancer Institute (NCI), The Leukemia and Lymphoma Society, Rising Tide Foundation
- Responsible party
- Sponsor-investigator, Robert Lowsky, Stanford University
- Investigators
- Ronald Levy, Principal investigator, Stanford UniversityMichael Khodadoust, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02927964
- Sponsor's protocol ID
- IRB-36750
- Other IDs
- NCI-2016-01065, IRB-36750, LYMNHL0135, R35CA197353
- Status last verified
- Sep 2023
- First submitted
- 6 Oct 2016
- Last updated
- 16 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Shree T, Haebe S, Czerwinski DK, Eckhert E, Day G, Sathe A, Grimes S, Frank MJ, Maeda LS, Alizadeh AA, Advani R, Hoppe RT, Long SR, Martin B, Ozawa MG, Khodadoust MS, Ji HP, Levy R. A clinical trial of therapeutic vaccination in lymphoma with serial tumor sampling and single-cell analysis. Blood Adv. 2024 Jan 9;8(1):130-142. doi: 10.1182/bloodadvances.2023011589.
PubMed 37939259Mooney KL, Czerwinski DK, Shree T, Frank MJ, Haebe S, Martin BA, Testa S, Levy R, Long SR. Serial FNA allows direct sampling of malignant and infiltrating immune cells in patients with B-cell lymphoma receiving immunotherapy. Cancer Cytopathol. 2022 Mar;130(3):231-237. doi: 10.1002/cncy.22531. Epub 2021 Nov 15.
PubMed 34780125