A Study of Durvalumab in Combination With Lenalidomide With and Without Dexamethasone in Adults With Newly Diagnosed Multiple Myeloma

Completed · Phase 1/Phase 2

Conditions studied: Multiple Myeloma

In brief

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 adults 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. \*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\*\* The study was placed on full clinical hold by the United States (US) Food and Drug Administration (FDA) on 05 Sep 2017. The decision by the FDA was based on data from non-Celgene-sponsored studies related to risks of anti-programmed cell death 1 (PD-1), pembrolizumab, in combination with immunomodulatory agents. As the result, the study was closed for further enrollment, and all subjects were discontinued from all study treatments (durvalumab, lenalidomide and dexamethasone). All subjects are being followed for second primary malignancies (SPMs), every 6 months for 5 years after the last subject has been enrolled as per protocol. After stopping data collection in the clinical database, any SPM events will continue to be recorded in the subject's source documents, and reported to Celgene Drug Safety.

Key facts

Study ID

NCT02685826

Run by

Celgene

People needed

56

Starts

2016-04-25

Expected to finish

2022-09-06

Last updated by the study team

2023-10-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Subjects must satisfy the following criteria to be enrolled into the study:
• Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements
• 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);
• (C) Calcium elevation (serum calcium >11.5 mg/dl )(>2.65 mmol/L)
• (R) Renal insufficiency (serum creatinine >2 mg/dl)(177 µmol/L or more) or creatinine clearance < 40 ml/min
• (A) Anemia (hemoglobin <10 g/dL or >2 g/dL below the lower limit of laboratory normal)
• (B) Bone lesions (lytic or osteopenic) one or more bone lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-computed tomography (PET-CT)
• one or more of the following biomarkers of malignancy:
• Clonal bone marrow plasma cell percentage ≥60%
• Abnormal serum free light-chain ratio ≥100 (involved kappa) or < 0.01 (involved lambda)
• >1 focal lesions detected by functional imaging including PET/CT and/or whole body magnetic resonance imaging (MRI)
• AND have measurable disease by protein electrophoresis analyses as defined by the following:
• Immunoglobulin G (IgG) MM: Serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dl or urine Mprotein level ≥ 200 mg/24 hours
• Immunoglobulin A (IgA) MM: Serum M-protein level ≥ 0.5 g/dl or urine M-protein level ≥ 200 mg/24 hours
• Immunoglobulin M (IgM) MM (IgM M-protein plus lytic bone disease documented by skeletal survey plain films): Serum M-protein level ≥ 1.0 g/dl or urine M-protein level ≥ 200 mg/24 hours
• Immunoglobulin D (IgD) MM: Serum M-protein level ≥ 0.05 g/dl or urine M-protein level ≥ 200 mg/24 hours
• Light chain MM: Serum M-protein level ≥ 1.0 g/dl or urine M-protein level ≥ 200 mg/24 hours
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

You may not qualify if…

• 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)
• Any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) < 1,000/μL
• Untransfused platelet count < 75,000 cells/μL
• Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase (SGOT/AST) or alanine aminotransferase (SGPT/ALT) > 2.5*upper limit of normal (ULN)
• Serum total bilirubin > 1.5*ULN or > 3.0 mg/dL for subjects with documented Gilbert's syndrome
• Corrected serum calcium >13.5 mg/dL (> 3.4 mmol/L)
• Renal failure requiring hemodialysis or peritoneal dialysis
• Any serious medical condition that places the subject at an unacceptable risk if he or she participates in this study. Examples of such a medical condition are, but are not limited to, subject with unstable cardiac disease as defined by: cardiac events such as myocardial infarction (MI) within the past 6 months, NYHA (New York Heart Association) heart failure class III-IV, uncontrolled atrial fibrillation or hypertension; subjects with conditions requiring chronic steroid or immunosuppressive treatment, such as rheumatoid arthritis, multiple sclerosis and lupus, that likely need additional steroid or immunosuppressive treatments in addition to the study treatment
• 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 following non-invasive malignancies:
• Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix
• Carcinoma in situ of the breast
• Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative
• Subjects is positive for human immunodeficiency virus (HIV); chronic or active hepatitis B or active hepatitis A, or C
• Subject had 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
• Subjects has history of organ or allogeneic stem cell transplantation
• Subjects who have had clinical evidence of central nervous system (CNS) or pulmonary leukostasis, disseminated intravascular coagulation, or CNS multiple myeloma, or plasma cell leukemia
• Known or suspected hypersensitivity to the excipients contained in the formulation of durvalumab, lenalidomide, or dexamethasone
• Major surgery (as defined by the investigator) within the 28 days prior to the first dose of study treatment
• Received prior treatment (for any reason)with a monoclonal antibody within 5 half-lives of initiating study treatment

Where it is running

• Winship Cancer Institute of Emory University — Atlanta, Georgia, United States
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Weill Medical College of Cornell University — New York, New York, United States
• Carolinas Healthcare System — Charleston, South Carolina, United States
• Swedish Medical Center — Seattle, Washington, United States
• Local Institution - 206 — Calgary, Alberta, Canada
• Tom Baker Cancer Center — Calgary, Alberta, Canada
• Cross Cancer Institute — Edmonton, Alberta, Canada
• Local Institution - 203 — Edmonton, Alberta, Canada
• British Columbia Cancer Agency — Vancouver, British Columbia, Canada
• Local Institution - 202 — Halifax, Nova Scotia, Canada
• Queen Elizabeth II Health Sciences Centre — Halifax, Nova Scotia, Canada
• Local Institution - 205 — Toronto, Ontario, Canada
• Princess Margaret Hospital and University of Toronto — Toronto, Ontario, Canada
• Local Institution - 901 — Copenhagen, Denmark
• Rigshospitalet University Hospital — Copenhagen, Denmark
• Local Institution - 903 — Odense, Denmark
• Odense Universitetshospital — Odense, Denmark
• Local Institution - 902 — Vejle, Denmark
• Vejle Hospital — Vejle, Denmark
• Helsinki UniversityCentral Hospital — Helsinki, Finland
• Local Institution - 801 — Helsinki, Finland
• Universitatsklinikum Essen — Essen, Germany
• University of Alabama Birmingham — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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