NCT03610061

A Trial of Radiotherapy and Durvalumab in DLBCL and FL

Phase I Dose Escalation Study of Radiotherapy and Durvalumab in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) and Follicular Lymphoma (FL): The RaDD Study

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: Austin Health · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The primary objective for this study is to determine the safety profile of radiotherapy and durvalumab, a PD-L1 inhibitor. Primary endpoint: Toxicity, drug pharmacokinetics (PK), maximum tolerated dose (MTD) and recommended phase two dose (RPTD) of simultaneous radiotherapy plus durvalumab in patients with relapsed or refractory DLBCL or FL. Secondary endpoints: * ORR * Progression-free survival * Overall survival Exploratory endpoints include description of biological effects of combination radiotherapy plus durvalumab (Imaging results, immune function, PK and PD-see 'research methodologies') and in the PET-Sub-Study, biodistribution of 89Zr Durvalumab and 89Zr-IAB22M2C.

Detailed description

Diffuse large B cell lymphoma (DLBCL) and Follicular Lymphoma (FL) are the most common non Hodgkin lymphomas. Standard first line treatment achieves cure in approximately half of patients. However 30% die from relapsed lymphoma. Durvalumab (an antibody which blocks programmed cell death ligand 1) and other immunotherapies fight cancer by blocking barriers to immune system activity. Immune control of lymphoma provides the prospect of cure, even when chemotherapy has failed. Radiotherapy has striking effects on the immune system and can boost responses to these immunotherapies. The effect of concurrent radiotherapy and durvalumab in DLBCL and FL is unproven. This study will evaluate the safety and effect of simultaneous radiotherapy plus durvalumab (a PD-L1 inhibitor) in relapsed DLBCL and FL patients.

Conditions

• Diffuse Large B Cell Lymphoma
• Follicular Lymphoma

Interventions

Type	Name	Description
DRUG	Durvalumab	All patients will receive: Day 1-Day 5: External Beam Radiotherapy to target site(s)-daily for 5 days (i.e. 5 fractions). D2: Commence durvalumab. Continue 4-weekly until disease progression. Patients can continue until a second radiological progression if clinical benefit is ongoing.
RADIATION	Radiotherapy	All patients will receive: Day 1-Day 5: External Beam Radiotherapy to target site(s)-daily for 5 days (i.e. 5 fractions). D2: Commence durvalumab. Continue 4-weekly until disease progression. Patients can continue until a second radiological progression if clinical benefit is ongoing.
RADIATION	Radiotherapy (cohort 6 only)	Cohort 6 patients (only) will receive: Day 8-Day 10: External Beam Radiotherapy to target site(s)- daily (ie. 5 further fractions to a total of 10 fractions)

Timeline

• Start date: 2018-11-01
• Primary completion: 2023-04-05
• Completion: 2024-04-08
• First posted: 2018-08-01
• Last updated: 2024-04-12

Locations

3 sites across 1 country: Australia