NCT03003520

A Study of Durvalumab in Combination With R-CHOP or Lenalidomide Plus R-CHOP in Previously Untreated High-Risk Diffuse Large B-Cell Lymphoma

A Phase 2, Open-label, Multicenter Study to Evaluate the Safety and Clinical Activity of Durvalumab in Combination With Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone (R-CHOP) or With Lenalidomide Plus R-CHOP (R2-CHOP) in Subjects With Previously Untreated, High-Risk Diffuse Large B-Cell Lymphoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 46 (actual)
• Sponsor: Celgene · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This Phase 2, two-arm, open-label study is designed to evaluate the safety, clinical activity, and predictive biomarkers of durvalumab in combination with R-CHOP or R2-CHOP, followed by durvalumab consolidation therapy in previously untreated subjects with high-risk diffuse large B-cell lymphoma (DLBCL). Induction treatment with R-CHOP (± lenalidomide) will last for a total of up to 6 to 8 treatment cycles (21 day cycles), and the total time on study treatment, including durvalumab consolidation, will last up to 12 months. On 05-Sep-2017, the US FDA has issued a Partial Clinical Hold on this study resulting in the discontinuation of enrollment into Arm B (Durvalumab + Lenalidomide + R-CHOP). After the US FDA Partial Clinical Hold, new eligible participants have been enrolled in Arm A (Durvalumab + R-CHOP).

Detailed description

This research study is conducted in participants with previously untreated, high-risk diffuse large B-cell lymphoma (DLBCL). Patients with high-risk DLBCL typically have insufficient therapeutic outcomes. Therefore, the addition of novel agents to the currently used induction therapy (R-CHOP) is a rational approach to improve therapeutic outcomes in this disease setting. Based on pre-clinical and clinical observations, it is hypothesized that durvalumab will have activity in DLBCL because the PD 1/PD L1 pathway is involved in the pathophysiology of DLBCL. In particular, the addition of durvalumab may augment the anti-tumor activity of R-CHOP against high-risk DLBCL sub-types. The safety of durvalumab has already been explored. However, as there is limited clinical experience with durvalumab in DLBCL, the study is divided into two stages: * A Safety Run-in Stage to evaluate the safety of the treatment combinations until at least 10 subjects are included in each of the two treatment arms * An Expansion Stage to analyze the clinical activity of the treatment combinations Results posted following Primary Outcome Completion date are based on a database cut-off of August 2, 2018.

Conditions

• Lymphoma, Large B-Cell, Diffuse

Interventions

Type	Name	Description
DRUG	Durvalumab	Durvalumab was supplied in single use vials as a liquid solution containing 500 mg (nominal) of durvalumab at a concentration of 50 mg/mL to be infused by intravenous (IV) injection. Day 1 of each treatment cycle (Induction Period and Consolidation Period) started with the administration of IV durvalumab followed by a 2-hour observation period post infusion.
DRUG	Rituximab	Subsequent to durvalumab infusion, rituximab was administered by IV. Rituximab administration could be split over 2 consecutive days according to local clinical practice. Rapid infusion of rituximab was not allowed in this clinical study.
DRUG	Doxorubicin	A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
DRUG	Vincristine	A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
DRUG	Cyclophosphamide	A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
DRUG	Prednisone	Prednisone was administered as an IV infusion or by mouth (PO) on Day 1, followed by PO administration on Days 2-5 of each cycle. Prednisone could be given prior to other drugs of the CHOP therapy. It was administered after lenalidomide dosing in the R2-CHOP treatment arm.
DRUG	Lenalidomide	Lenalidomide was administered orally in capsule form on Days 1-14 of the DUR+R2-CHOP treatment arm only.

Timeline

• Start date: 2017-02-28
• Primary completion: 2022-04-24
• Completion: 2022-04-24
• First posted: 2016-12-28
• Last updated: 2023-05-22
• Results posted: 2019-09-16

Locations

20 sites across 5 countries: United States, Austria, Denmark, Estonia, United Kingdom

Regulatory

• FDA-regulated drug study