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 : Recruiting
First Posted : December 28, 2016
Last Update Posted : December 4, 2017
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.
Patients with non-ABC subtype (determined by gene expression profiling) will be allocated to Arm A while patients with ABC (activated B-cell type) subtype will be allocated to Arm B. Approximately 120 patients may be enrolled and assigned into the appropriate treatment arms dependent upon their cell of origin status.
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.
|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 backbone) 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 significantly augment the anti-tumor activity of R-CHOP against high-risk DLBCL subtypes.
There are different subtypes of DLBCL which are distinguished by their Cell of Origin (ABC, GCB, unclassifiable). About a third of DLBCL is of the ABC subtype and as those patients have a worse outcome when treated with R-CHOP, lenalidomide plus R-CHOP (R2-CHOP) will be used for patients with the ABC subtype.
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 for a total of 20 subjects
- An Expansion Stage to analyze the clinical activity of the treatment combinations in up to 100 additional subjects
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||120 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 :||June 22, 2021|
|Estimated Study Completion Date :||July 1, 2024|
Experimental: Arm A (non-ABC DLBCL): 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 (ABC DLBCL): 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.
- Progression Free Survival at 24 months [ Time Frame: Up to 24 months after last patient is enrolled ]Subjects who have not experienced disease progression or death within 24 months after start of study treatment
- 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
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
|Contact: Associate Director Clinical Trial Disclosureemail@example.com|
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|Study Director:||Oliver Manzke, Medical Doctor||Celgene Corporation|