SHS_492351 BENW CCLG 16153

A Phase 1b Multicenter, Open-label Study to Determine the Recommended Dose and Regimen of Durvalumab (MEDI4736) (DUR) in Combination With Lenalidomide (LEN) With and Without Low-dose Dexamethasone (Dex) in Subjects With Newly Diagnosed Multiple Myeloma (NDMM)

This is a multicenter, open-label, Phase 1/2 study to determine the recommended dose and regimen of durvalumab in combination with lenalidomide (LEN) with and without dexamethasone (dex) in subjects with Newly diagnosed multiple myeloma (NDMM). The study will consist of a dose-finding phase as well as a parallel dose-expansion phase to determine the optimal regimen.

Select Inclusion Criteria:

Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
Subject must have documented diagnosis with previously untreated (for cohort C, the induction and consolidation treatment along with the first Autologous stem cell transplantation (ASCT) are allowed), symptomatic Multiple Myeloma (MM) as defined by the criteria below:
MM diagnostic criteria (all 3 required);
Monoclonal protein present in the serum and/or urine
Clonal bone marrow plasma cells ≥10% or biopsy-proven bony or extramedullary plasmacytoma
Any one or more of the following myeloma defining events:
one or more of the following Myeloma-related organ dysfunction (at least one of the following): Calcium elevation (serum calcium >11.5 mg/dl ); renal insufficiency (serum creatinine >2 mg/dl)or creatinine clearance < 40 ml/min; anemia (hemoglobin <10 g/dl or >2 g /dL below the lower limit of laboratory normal); bone lesions (lytic or osteopenic) one or more bone lesions on skeletal radiography, Computed tomography (CT), or PET-CT
One or more of the following biomarkers of malignancy
AND have measurable disease by protein electrophoresis analyses as defined by specific measures listed in the protocol

Select Exclusion Criteria:

The presence of any of the following will exclude a subject from enrollment:
Previous treatment with anti-myeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid (ie, less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 14 days of Cycle 1 Day 1), for Cohort C, the induction and consolidation treatment along with the first Autologous stem cell transplantation (ASCT) are allowed)
Renal failure requiring hemodialysis or peritoneal dialysis
Any serious medical condition
Peripheral neuropathy ≥ Grade 2
Primary AL (immunoglobulin light-chain) amyloidosis and myeloma complicated by amyloidosis
Prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 5 years with the exception of the certain non-invasive malignancies
Positive for human immunodeficiency virus (HIV); chronic or active hepatitis B or active hepatitis A, or C
Prior exposure to immunotherapy, including, but not limited to, other anti- CTLA-4,anti-PD-1, anti-PD-L1 monoclonal antibody or inhibitor, cell-based therapies, or cancer vaccines
History of organ or allogeneic stem cell transplantation
Clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma, or plasma cell leukemia
Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study treatment. The following are exceptions to this criterion:
Intranasal, inhaled, topical or local steroid injections
Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent;
Active or prior documented autoimmune or inflammatory disorders
History of primary immunodeficiency
Subject has incidence of gastrointestinal disease that may significantly alter the absorption of LEN
Phase Ib
NCT02685826
Cancer, All Other
Hematologic
William Bensinger, M.D.
Celgene Corporation
Tenzin Tsomo
  • Swedish Medical Center