A Study of Durvalumab in Combination With R-CHOP or Lenalidomide Plus R-CHOP in Previously Untreated High-Risk Diffuse Large B-Cell Lymphoma
NCT ID: NCT03003520
Last Updated: 2023-05-22
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
46 participants
INTERVENTIONAL
2017-02-28
2022-04-24
Brief Summary
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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).
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Detailed Description
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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
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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DUR + R-CHOP
On Day 1 of each 21-day cycle, participants received durvalumab 1125 mg intravenously (IV) followed by R-CHOP (IV rituximab 375 mg/m\^2, doxorubicin 50 mg/m\^2, vincristine 1.4 mg/m\^2 (maximum dose of 2.0 mg total), and cyclophosphamide 750 mg/m\^2); Participants also were administered daily oral or IV prednisone/prednisolone 100 mg from Day 1 to 5. Induction treatment continued for a total of 6-8 cycles.
Participants who achieve a complete response or partial response continue with consolidation therapy treatment consisting of durvalumab monotherapy 1500 mg by IV on Day 1 of each 28-day cycle for up to a total of 12 months.
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.
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.
Doxorubicin
A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
Vincristine
A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
Cyclophosphamide
A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
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.
DUR + R2-CHOP
Participants start the study on durvalumab in combination with R-CHOP (as described in Arm DUR + R-CHOP). Based on their DLBCL Cell-of-Origin subtype (test typically done between cycles 1 and 2), participants with ABC subtype continue the study taking durvalumab in combination with R2-CHOP. On Day 1 of each 21-day cycle, participants received durvalumab 1125 mg intravenously (IV) followed by R-CHOP. Participants were also administered daily oral or IV prednisone/prednisolone 100 mg from Day 1 to 5. In addition, a daily oral lenalidomide 15 mg was administered from Day 1 to 14 of each 21-day cycle. Induction treatment continued for a total of 6-8 cycles.
Participants who achieve a complete response or partial response continue with consolidation therapy treatment consisting of durvalumab monotherapy 1500 mg by IV on Day 1 of each 28-day cycle for up to a total of 12 months.
Enrollment into Arm B was discontinued.
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.
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.
Doxorubicin
A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
Vincristine
A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
Cyclophosphamide
A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
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.
Lenalidomide
Lenalidomide was administered orally in capsule form on Days 1-14 of the DUR+R2-CHOP treatment arm only.
Interventions
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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.
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.
Doxorubicin
A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
Vincristine
A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
Cyclophosphamide
A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.
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.
Lenalidomide
Lenalidomide was administered orally in capsule form on Days 1-14 of the DUR+R2-CHOP treatment arm only.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Ann Arbor stage 3 or 4 or stage 2 with bulky disease
3. High or high-intermediate disease risk.
4. No prior anti-lymphoma treatment.
5. Subject is willing and able to undergo biopsy.
6. Investigator considers R-CHOP immunochemotherapy appropriate.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
8. Adequate hematology laboratory results (absolute neutrophil count ≥ 1.5 \* 10\^9/L, platelet count ≥ 75 \* 10\^9/L, hemoglobin ≥ 10.0 g/dL).
9. 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).
10. Bi-dimensionally measurable disease (\> 2.0 cm).
11. Subject is using effective contraception.
Exclusion Criteria
2. Composite lymphoma or transformed lymphoma.
3. Primary or secondary Central Nervous System involvement by lymphoma.
4. Seropositive or active viral infection with hepatitis B virus, human immunodeficiency virus or hepatitis C virus.
5. History of other malignancies, unless disease-free for ≥ 5 years.
6. Left ventricular ejection fraction \< 50%.
7. Peripheral neuropathy ≥ Grade 2.
8. Prior use of lenalidomide, or monoclonal antibodies against CTLA-4, PD-1, or PD-L1.
9. High risk of developing thromboembolic events, who are unwilling to take venous thromboembolism prophylaxis.
10. Active or prior documented autoimmune or inflammatory disorders within the past 3 years.
11. Current or prior use of immunosuppressive medication within 28 days before start of treatment.
18 Years
ALL
No
Sponsors
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Celgene
INDUSTRY
Responsible Party
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Principal Investigators
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Bristol-Myers Squibb
Role: STUDY_DIRECTOR
Bristol-Myers Squibb
Locations
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Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
Parkview Research Center
Fort Wayne, Indiana, United States
Mayo Clinic
Rochester, Minnesota, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
University of Rochester Medical Center
Rochester, New York, United States
Mid Ohio Oncology Hematology Inc
Columbus, Ohio, United States
Swedish Cancer Institute
Seattle, Washington, United States
Innsbruck Medical University Department of Internal Medicine
Innsbruck, , Austria
Landeskrankenhaus Salzburg
Salzburg, , Austria
Hanusch Krankenhaus
Vienna, , Austria
Local Institution - 101
Vienna, , Austria
Medical University of Vienna Internalmedicine 1, Hematology
Vienna, , Austria
Aarhus Sygehus
Arhus C, , Denmark
Rigshospitalet, Kobenhavns Universitet - Centre for Clinical Intervention Research - The Copenhagen
Copenhagen, , Denmark
Odense Universitetshospital
Odense C, , Denmark
(North Estonia Medical Centre) - Onkoloogia-ja Hematoloogiakliinik
Tallinn, , Estonia
Tartu University Hospital
Tartu, , Estonia
University Hospital Birmingham
Birmingham, , United Kingdom
Royal Marsden Hospital
London, , United Kingdom
Oxford University Hospitals NHS Trust- Churchill Hospital-Oxford Centre for Respiratory Medicine
Oxford, , United Kingdom
Countries
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Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Related Links
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BMS Clinical Trial Information
BMS Clinical Trial Patient Recruiting
Other Identifiers
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2015-005173-20
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
MEDI4736-DLBCL-001
Identifier Type: -
Identifier Source: org_study_id
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