MEDI4736-DLBCL-001 Phase 2 High-Risk Diffuse Large B-Cell Lymphoma

• Research type

  Research Study

• Full title

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

• IRAS ID

  215854

• Contact name

  Nagesh Kalakonda

• Contact email

  nageshk@liv.ac.uk

• Sponsor organisation

  Celgene International II Sàrl

• Eudract number

  2015-005173-20

• Clinicaltrials.gov Identifier

  NCT03003520

• Clinicaltrials.gov Identifier

  32348, NIHR Clinical Research Network reference number

• Duration of Study in the UK

  7 years, 3 months, 23 days

• Research summary

  This is a Phase 2, open-label, multicentre study evaluating the safety and clinical activity of Durvalumab in combination with two separate groups of drugs:

  • R-CHOP group (Arm A): Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone
  • R2 CHOP group (Arm B): Lenalidomide plus R-CHOP

  All patients will be treated with durvalumab combined with R-CHOP during Cycle 1 of induction therapy. Based on their DLBCL cell-of-origin (COO) subtype before start of Cycle 2, patients will be allocated to one of two treatment arms from Cycle 2 onwards:
  Induction Therapy (21-day cycles)
  • Arm A: Durvalumab in combination with R-CHOP

  Durvalumab 1125 mg intravenously (IV) on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R-CHOP (IV rituximab, doxorubicin, vincristine, and
  cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5).

  • Arm B: Durvalumab in combination with R2-CHOP

  Durvalumab 1125 mg IV on Day 1 of each 21-day cycle in combination with 6 to 8 cycles R2-CHOP (IV rituximab, doxorubicin, vincristine and cyclophosphamide on Day 1; daily oral/IV prednisone/prednisolone from Day 1 to 5; daily oral lenalidomide
  15 mg from Day 1 to 14) from Cycle 2 until end of induction therapy (Cycle 6 or Cycle 8), or starting Cycle 1 if ABC subtype is identified prior to Cycle 1 Day 1 (C1D1).
  Consolidation Therapy (28-day cycles)
  • Arm A and Arm B:

  Durvalumab 1500 mg IV on Day 1 of each 28-day cycle for up to a total of 12 months from C1D1.

  The study is divided into two stages:
  • A Safety Run-in Stage to evaluate the safety of the treatment combinations until at least 10 patients are included in each of the two treatment arms for a total of 20 patients in the safety run-in stage

  • An Expansion Stage to analyse the clinical activity of the treatment combinations in up to 100 additional patients in the expansion stage
  Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of white blood cell responsible for producing antibodies. DLBCL is the most common type of non-Hodgkin’s lymphoma (NHL) that accounts for approximately 31% of all newly diagnosed malignant lymphomas. It is characterised by large tumour cells and aggressive clinical behaviour.

  In most countries worldwide, the standard of care treatment for newly diagnosed DLBCL consists of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy in combination with the anti-CD20 monoclonal antibody rituximab (R-CHOP). In a study comparing R-CHOP with CHOP as front-line therapy in elderly patients with DLBCL, treatment with R-CHOP achieved a 5-year event-free survival (EFS) of 47%, a 5-year progression free survival (PFS) of 54%, and a 5-year overall survival (OS) of 58%.

  Approximately 120 patients with previously untreated, high-risk DLBCL will be enroled from Europe and the US. The study consists of a Screening period (up to 28 days before first dose of study treatment), a treatment period (up to a total of 12 months from first dose) and a follow-up period (up to 5 years after the last patient is enroled into Arm B).
  Patients may continue study treatment until their DLBCL progresses or unacceptable toxicity or if they choose to withdraw from the study. After the study ends, patients will receive Standard of Care.
  There will be several procedures performed in this study some include, ECG (a recording of your hearts electrical activity), bone marrow aspiration/biopsy (bone marrow will be drawn with a needle), x-ray, CT scan, PET and MUGA scans.

• REC name

  Yorkshire & The Humber - Leeds West Research Ethics Committee

• REC reference

  17/YH/0022

• Date of REC Opinion

  24 May 2017

• REC opinion

  Further Information Favourable Opinion