Phase 2
N=46
A Study of Durvalumab in Combination With R-CHOP or Lenalidomide Plus R-CHOP in Previously Untreated High-Risk Diffuse Large B-Cell Lymphoma
Lymphoma, Large B-Cell, Diffuse
Bottom Line
View on ClinicalTrials.gov: NCT03003520 ↗Enrolled (actual)
46
Serious AEs
52.2%
Results posted
Sep 2019
Primary outcome: Primary: Percentage of Participants Who Achieved a Complete Response (CR) at the End of Induction Therapy — 54.1; 66.7 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Durvalumab (Drug); Rituximab (Drug); Doxorubicin (Drug); Vincristine (Drug); Cyclophosphamide (Drug); Prednisone (Drug); Lenalidomide (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Celgene
- Primary completion
- Apr 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Achieved a Complete Response (CR) at the End of Induction Therapy |
54.1; 66.7 | — |
| SECONDARY Percentage of Participants Who Responded During Induction and Continued Into Consolidation Therapy (Database Cutoff Date: 02-Aug-2018) |
67.6; 66.7 | — |
| SECONDARY Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) CD8 T-Cell Density |
67; 64 | >0.99 |
| SECONDARY Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) Programmed Death Ligand - 1 (PDL1) Total Percentage |
75; 20 | 0.0403 sig |
| SECONDARY Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for Immunohistochemistry (IHC) Programmed Death Ligand - 1 (PDL1) Percentage of Tumor Cells |
64; 56 | >0.99 |
| SECONDARY Percentage of Participants Who Achieved a Clinical Response in the Biomarker Subpopulation for the Interferon Gamma Score (IFNG-Score) From Ribonucleic Acid (RNA)-Sequencing Data |
43; 60 | 0.662 |
| SECONDARY Participants With Treatment Emergent Adverse Events (TEAE) |
43; 3; 33; 3; 40; 3 | — |
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).
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.
Data sourced from ClinicalTrials.gov (NCT03003520). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.