Non Hodgkin Lymphoma Clinical Trial
A Study of Durvalumab in Combination With R-CHOP or Lenalidomide Plus R-CHOP in Previously Untreated High-Risk Diffuse Large B-Cell Lymphoma
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).
Full 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.
Eligibility Criteria
Inclusion Criteria:
CD20+Diffuse Large B-Cell Lymphoma.
Ann Arbor stage 3 or 4 or stage 2 with bulky disease
High or high-intermediate disease risk.
No prior anti-lymphoma treatment.
Subject is willing and able to undergo biopsy.
Investigator considers R-CHOP immunochemotherapy appropriate.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
Adequate hematology laboratory results (absolute neutrophil count ≥ 1.5 * 10^9/L, platelet count ≥ 75 * 10^9/L, hemoglobin ≥ 10.0 g/dL).
Adequate biochemistry laboratory results (aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3.0 * upper limit of normal; bilirubin ≤ 2.0 mg/dL; creatinine clearance of ≥ 40 mL/min).
Bi-dimensionally measurable disease (> 2.0 cm).
Subject is using effective contraception.
Exclusion Criteria:
Diagnosis of lymphoma other than Diffuse Large B-Cell Lymphoma.
Composite lymphoma or transformed lymphoma.
Primary or secondary Central Nervous System involvement by lymphoma.
Seropositive or active viral infection with hepatitis B virus, human immunodeficiency virus or hepatitis C virus.
History of other malignancies, unless disease-free for ≥ 5 years.
Left ventricular ejection fraction < 50%.
Peripheral neuropathy ≥ Grade 2.
Prior use of lenalidomide, or monoclonal antibodies against CTLA-4, PD-1, or PD-L1.
High risk of developing thromboembolic events, who are unwilling to take venous thromboembolism prophylaxis.
Active or prior documented autoimmune or inflammatory disorders within the past 3 years.
Current or prior use of immunosuppressive medication within 28 days before start of treatment.
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There are 19 Locations for this study
Gilbert Arizona, 85234, United States
Fort Wayne Indiana, 46845, United States
Rochester Minnesota, 55905, United States
Buffalo New York, 14263, United States
Rochester New York, 14642, United States
Columbus Ohio, 43219, United States
Seattle Washington, 98104, United States
Innsbruck , 6020, Austria
Salzburg , 5020, Austria
Vienna , 1190, Austria
Vienna , 1190, Austria
Wien , 1140, Austria
Arhus C , DK-80, Denmark
Copenhagen , 2100, Denmark
Odense C , DK500, Denmark
Tallinn , 13419, Estonia
Tartu , 51014, Estonia
Birmingham , B15 2, United Kingdom
London , SW3 6, United Kingdom
Oxford , 0X3 7, United Kingdom
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