A Phase 2, Open-label, Multicenter study to Evaluate the Safety and Clinical Activity of Durvalumab in Combination with Rituximab, Cyclophosphamide, Doxorubicin, Vincrestine, Prednisone (R-CHOP) or with Lenalidomide plus R CHOP (R2 CHOP) in Subjects with Previously Untreated, High Risk Diffuse Large B Cell Lymphoma

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.

Cancer (Oncology), Cancer (Oncology) - Lymphoma
Krish Patel, MD

Swedish Cancer Institute

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. ECOG performance status of 0-2.
  8. Adequate hematology laboratory results (absolute neutrophil count ≥ 1.5 x 10^9/L, platelet count ≥ 75 x 10^9/L, hemoglobin ≥ 10.0 g/dL).
  9. Adequate biochemistry laboratory results (AST/SGOT and ALT/SGPT ≤ 3.0 x 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.
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