A Study of Durvalumab in Combination With R-CHOP or Lenalidomide Plus R-CHOP in Previously Untreated High-Risk Diffuse Large B-Cell Lymphoma
Condition: Lymphoma, Large B-Cell, Diffuse
MeSH terms: Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse
Intervention: Durvalumab; Rituximab; Doxorubicin; Vincristine; Cyclophosphamide; Prednisone; Lenalidomide
Intervention description: 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.; 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.; A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.; A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.; A component of the CHOP therapy administered by IV. CHOP therapy was administered following rituximab.; 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 was administered orally in capsule form on Days 1-14 of the DUR+R2-CHOP treatment arm only.
Intervention MeSH terms: Prednisone; Prednisolone; Cyclophosphamide; Rituximab; Doxorubicin; Vincristine; Lenalidomide; Durvalumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lymphoma; Diffuse-large B-Cell Lymphoma; Durvalumab; Anti-PD-L1 Antibody; MEDI4736; Immune Checkpoint; Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisone/Prednisolone; Lenalidomide

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:

          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.