A Study of Durvalumab in Combination With R-CHOP or Lenalidomide Plus R-CHOP in Previously Untreated High-Risk Diffuse Large B-Cell Lymphoma

• Status: Active, not recruiting
• Trial end date: 2023-03-13
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Celgene
• Treatments: Antibodies, Monoclonal; Cyclophosphamide; Doxorubicin; Durvalumab; Lenalidomide; Liposomal doxorubicin; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Prednisone; Rituximab; Thalidomide; Vincristine

Criteria

Inclusion Criteria:

1. CD20+Diffuse Large B-Cell Lymphoma.

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:

1. Diagnosis of lymphoma other than Diffuse Large B-Cell Lymphoma.

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.