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

Phase 1

Completed

• Conditions: Marginal Zone Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Recurrent Follicular Lymphoma; Mantle Cell Lymphoma; Grade 3a Follicular Lymphoma; Refractory Follicular Lymphoma
• Interventions: Drug: Ibrutinib; Radiation: Radiation Therapy; Drug: TLR9 Agonist SD-101

• Registration Number: NCT02927964
• Lead Sponsor: Robert Lowsky

Brief 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 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

Study Timeline

• Study First Submitted: 2016-10-06
• Study First Submitted QC: 2016-10-06
• Study First Posted: 2016-10-07
• Study Start: 2016-11-07
• Primary Completion: 2023-05-18
• Study Completion: 2023-05-18
• Status Verified: 2023-09
• Results First Submitted: 2024-05-20
• Results First Submitted QC: 2024-10-11
• Last Update Submitted: 2024-10-11
• Results First Posted: 2024-10-16
• Last Update Posted: 2024-10-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase 1b -SD-101 3mg	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.
Phase 1b -SD-101 3mg	Radiation Therapy	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.
Phase 1b -SD-101 3mg	TLR9 Agonist SD-101	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.

Primary Outcome Measures

Name	Time	Method
Number of Dose-limiting Toxicity Assessed Using Common Terminology Criteria for Adverse Events Version 4.0 (Phase Ib)	Up to 24 months	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.
Tumor Response Rates (Phase II)	Up to 24 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.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival (Phase II)	Up to 24 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.

Trial Locations

Locations (1)

Stanford University, School of Medicine; 🇺🇸 Palo Alto, California, United States