A Study of Durvalumab in Combination With R-CHOP or Lenalidomide Plus R-CHOP in Previously Untreated High-Risk Diffuse Large B-Cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT03003520|
Recruitment Status : Active, not recruiting
First Posted : December 28, 2016
Last Update Posted : July 3, 2018
This Phase 2, two-arm, open-label study is designed to evaluate the safety, clinical activity, predictive biomarkers and pharmacokinetics/ pharmacodynamics of durvalumab in combination with R-CHOP (Arm A) or R2-CHOP (Arm B), followed by durvalumab consolidation therapy in previously untreated subjects with high-risk DLBCL. Induction treatment with R-CHOP (± Lenalidomide) will last for a total of up to 6 to 8 treatment cycles (21 days cycle), 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 enrolment into Arm B (Durvalumab + Lenalidomide + R-CHOP). After the US FDA Partial Clinical Hold, new eligible subjects have been enrolled in Arm A (Durvalumab + R-CHOP).
|Condition or disease||Intervention/treatment||Phase|
|Lymphoma, Large B-Cell, Diffuse||Drug: Durvalumab Drug: Rituximab Drug: Doxorubicin Drug: Vincristine Drug: Cyclophosphamide Drug: Prednisone Drug: Lenalidomide||Phase 2|
This research study is conducted in patients 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 subtypes.
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
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||46 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||February 28, 2017|
|Estimated Primary Completion Date :||July 24, 2018|
|Estimated Study Completion Date :||March 13, 2023|
Experimental: Arm A: Durvalumab in combination with R-CHOP
Durvalumab 1125 mg intravenously (IV) on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R-CHOP (IV rituximab, doxorubicin, vincristine, and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5) followed by durvalumab monotherapy for up to a total of 12 months after start of study treatment.
Experimental: Arm B: Durvalumab in combination with R2-CHOP
Durvalumab 1125 mg IV on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R2-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5; daily oral lenalidomide 15 mg from Day 1 to 14) from Cycle 2 until end of induction therapy (Cycle 6 or Cycle 8), or starting Cycle 1 if ABC subtype is identified prior to Cycle 1 Day 1 (C1D1) followed by durvalumab monotherapy for up to a total of 12 months after start of study treatment.
- Complete Response Rate [ Time Frame: Up to 6 months after first dose of any IP ]Subjects achieving a Complete Response at the end of induction therapy.
- Treatment-Emergent Adverse Events (AEs) [ Time Frame: Up to 15 months after last patient is enrolled ]Number of participants with adverse event
- Clinical response to study treatment in biomarker-defined subpopulations [ Time Frame: Up to 24 months after last patient is enrolled ]Identification and development of biomarkers predictive of clinical response to study treatment
- Rate of subjects who continue into consolidation therapy [ Time Frame: up to 6 months after first dose of any IP ]Subjects eligible to continue into consolidation therapy after achieving a Complete Response or (good) Partial Response after induction therapy.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03003520
|United States, Arizona|
|Banner MD Anderson Cancer Center|
|Gilbert, Arizona, United States, 85234|
|United States, Indiana|
|Parkview Research Center|
|Fort Wayne, Indiana, United States, 46845|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|United States, New York|
|Roswell Park Cancer Institute|
|Buffalo, New York, United States, 14263|
|University of Rochester Medical Center|
|Rochester, New York, United States, 14642|
|United States, Ohio|
|Mid Ohio Oncology Hematology Inc|
|Columbus, Ohio, United States, 43219|
|United States, Washington|
|Swedish Cancer Institute|
|Seattle, Washington, United States, 98104|
|Innsbruck Medical University Department of Internal Medicine|
|Innsbruck, Austria, 6020|
|Salzburg, Austria, 5020|
|Medical University of Vienna Internalmedicine 1, Hematology|
|Vienna, Austria, 1190|
|Wien, Austria, 1140|
|Arhus C, Denmark, DK-8000|
|Rigshospitalet, Kobenhavns Universitet - Centre for Clinical Intervention Research - The Copenhagen|
|Copenhagen, Denmark, 2100|
|Odense C, Denmark, DK5000|
|(North Estonia Medical Centre) - Onkoloogia-ja Hematoloogiakliinik|
|Tallinn, Estonia, 13419|
|Tartu University Hospital|
|Tartu, Estonia, 51014|
|University Hospital Birmingham|
|Birmingham, United Kingdom, B15 2TH|
|Royal Marsden Hospital|
|London, United Kingdom, SW3 6JJ|
|Oxford University Hospitals NHS Trust- Churchill Hospital-Oxford Centre for Respiratory Medicine|
|Oxford, United Kingdom, 0X3 7LE|
|Study Director:||Oliver Manzke, Medical Doctor||Celgene Corporation|