Multiple MyelomaPhase 1/2NCT02685826
A Study of Durvalumab in Combination With Lenalidomide With and Without Dexamethasone in Adults With Newly Diagnosed Multiple Myeloma
A Phase 1/2 study testing Durvalumab, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Celgene at 54 sites in 8 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- Durvalumab, Lenalidomide and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 54 sitesin 8 countries
- Study dates
- 25 Apr 2016to 6 Sep 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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);
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- 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:
- 1. 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)
- 2. 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
- 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
- 6. Females of childbearing potential (FCBP) must:
- Have two negative pregnancy tests as verified by the investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.
- She must either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and be source documented) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study treatment, during the study therapy (including dose interruptions), and for 90 days after discontinuation of study treatment.
- Refrain from egg cell and blood donation for 90 days after the final dose of durvalumab.
- 7. Male subjects must :
- Practice true abstinence (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a FCBP while participating in the study, during dose interruptions and for at least 90 days following study treatment discontinuation, even if he has undergone a successful vasectomy.
- Refrain from sperm and blood donation for at least 90 days after the final dose of durvalumab.
- 8. For Cohort A subject must be transplant non-eligible (TNE) and meet at least one of the following high risk factors:
- Cytogenetic abnormalities finding in malignant myeloma clone with t(4; 14); and / or del(17p); and / or 1q amplification; and / or t(14:16); or
- International Staging System (ISS) Stage III; or
- Serum lactate dehydrogenase (LDH) > 2*ULN (upper limit of normal).
- 9. For Cohort B subject must be ≥ 65 years of age at the time of signing the informed consent form (ICF) and transplant non-eligible (TNE); excluding the subjects who meet the Cohort A criteria.
- 10. For Cohort C subject must be after first autologous stem cell transplantation (ASCT) for NDMM and meet the following criteria:
- Have a post-transplant response as Partial response (PR) or better at the time of enrollment to this study;
- Have one of the following high risk factors at the time of NDMM diagnosis;
- Cytogenetic abnormalities finding in malignant myeloma clone with t(4; 14); and / or del(17p); and / or 1q amplification; and / or t(14; 16); or
- ISS stage III; or
- Serum LDH > 2*ULN;
- Minimal residual disease (MRD) positive (defined as more than 1 malignant cell in 105 cells) measured by ClonoSIGHT™NGS assay of a BMA sample) at the time of enrollment to this study; BMA sample collected at the time of multiple myeloma diagnosis, prior to induction therapy available for central MRD assessment by ClonoSIGHT™NGS assay
Who cannot join
- 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)
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- 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
- Use of any investigational agents within 28 days or 5 half-lives (whichever is longer) of initiating study treatment
- 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 (eg, intra-articular injection);
- Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent;
- Steroids as premedication for hypersensitivity reactions (eg, computed tomography (CT) scan premedication);
- Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (eg, colitis, Crohn's disease], diverticulitis with the exception of a prior episode that has resolved or diverticulosis, celiac disease, irritable bowel disease, or other serious gastrointestinal chronic conditions associated with diarrhea; systemic lupus erythematosus; Wegener's syndrome [granulomatosis with polyangiitis); myasthenia gravis; Graves' disease; rheumatoid arthritis; hypophysitis, uveitis) within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
- Subjects with vitiligo or alopecia;
- Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement; or
- Subjects with psoriasis not requiring systemic treatment;
- History of primary immunodeficiency
- Subject has incidence of gastrointestinal disease that may significantly alter the absorption of LEN
- Receipt of live, attenuated vaccine within 30 days prior to the first dose of durvalumab
- Unable or unwilling to undergo protocol required thromboembolism prophylaxis(for Cohort C, this will be only for the subjects who have a history of VTE)
- Females who are pregnant, nursing or breastfeeding, or intend to become pregnant during the participation to the study
- Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
- Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
- Any condition that confounds the ability to interpret data from the study
Trial locations and contacts
54 sites in 8 countries.
54 sites in 8 countries
Spain11 sites
Hopsital Germans Trias I Pujol
Badalona, 08918
Hospital 12 de Octobre
Madrid, 28041
Local Institution - 505
Madrid, 28041
Clinica Universitaria de Navarra
Pamplona, 31008
Local Institution - 501
Pamplona, 31008
Hospital Universitario de Salamanca
Salamanca, 37007
Local Institution - 503
Salamanca, 37007
Hospital Doctor Peset
Valencia, 46017
Local Institution - 506
Valencia, 46017
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, 46026
Local Institution - 504
Valencia, 46026
Italy10 sites
Local Institution - 405
Bologna, 40138
Policlinico S. Orsola
Bologna, 40138
I.R.C.C.S. Policlinico San Matteo - Universita di Pavia
Pavia, 27100
Local Institution - 402
Pavia, 27100
Local Institution - 403
Reggio Emilia, 42100
Servizio di Ematologia, A.O. - Arcispedale S.Maria Nuova
Reggio Emilia, 42100
Local Institution - 404
Rome, Roma, 168
Policlinico Agostino Gemelli
Rome, 00168
Azienda Ospedaliera San Giovanni Battista - Ospedale Molinette
Torino, 10126
Local Institution - 406
Torino, 10126
Canada9 sites
Local Institution - 206
Calgary, Alberta, T2N 4N2
Tom Baker Cancer Center
Calgary, Alberta, T2N 4N2
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Local Institution - 203
Edmonton, Alberta, T6G 1Z2
Local Institution - 202
Halifax, Nova Scotia, B3H 2Y9
Queen Elizabeth II Health Sciences Centre
Halifax, Nova Scotia, B3H 2Y9
Local Institution - 205
Toronto, Ontario, M5G 2M9
Princess Margaret Hospital and University of Toronto
Toronto, Ontario, M5G 2M9
British Columbia Cancer Agency
Vancouver, British Columbia, V5Z 4E6
United States7 sites
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
University of Alabama Birmingham
Birmingham, Alabama, 35294-000
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Carolinas Healthcare System
Charleston, South Carolina, 28203
Weill Medical College of Cornell University
New York, New York, 10065
Swedish Medical Center
Seattle, Washington, 98104
Denmark6 sites
Local Institution - 901
Copenhagen, 2100
Rigshospitalet University Hospital
Copenhagen, 2100
Local Institution - 903
Odense, 5000
Odense Universitetshospital
Odense, 5000
Local Institution - 902
Vejle, 7100
Vejle Hospital
Vejle, 7100
Germany5 sites
Universitatsklinikum Essen
Essen, 45122
Local Institution - 304
Koblenz, 56068
Praxis fuer Haematologie und Onkologie Koblenz
Koblenz, 56068
Local Institution - 302
Tübingen, 72076
University of Tubingen
Tübingen, 72076
Netherlands4 sites
Local Institution - 704
Amsterdam, 1081 HV
VU Medical Center
Amsterdam, 1081 HV
Erasmus Medical Center
Rotterdam, 3015 CN
Local Institution - 703
Rotterdam, 3015 CN
Finland2 sites
Helsinki UniversityCentral Hospital
Helsinki, 00029 HUS
Local Institution - 801
Helsinki, 00029 HUS
About this study
Official title: A Phase 1/2 Multicenter, Open-label Study to Determine the Recommended Dose and Regimen of Durvalumab (MEDI4736) in Combination With Lenalidomide (LEN) With and Without 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 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.
Read more
******************
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.
Read the detailed description
The dose-finding phase will determine recommended dose (RD) for durvalumab in combination with lenalidomide (LEN) with and without dexamethasone (dex) in a 28-day treatment cycle. Three treatment Cohorts (A, B, and C) will be enrolled in parallel:
- Cohort A: durvalumab + LEN + dex in high risk transplant non-eligible (TNE) newly diagnosed multiple myeloma (NDMM) participants;
- Cohort B: durvalumab + LEN + dex (dex for up to 12 cycles) in ≥ 65 years old TNE NDMM participants who are not high risk;
- Cohort C: durvalumab + LEN as maintenance in post-transplant high risk NDMM participants.
Based on experience with durvalumab for other indications, the initial dose of durvalumab will be 1500 mg for each treatment cohort. The dose of durvalumab might be de-escalated to 750 mg level.
The dose of LEN will be 25 mg (adjustable per the creatinine clearance [CrCl] value) on Days 1 to 21 of each 28-day treatment cycle for participants in Cohort A and B. The dose of LEN will be 10 mg on Days 1 to 21 of each 28-day treatment cycle for participants in Cohort C.
The dose of dex will be 40 mg/day (for participants ≤ 75 years old) or 20 mg/day (for participants > 75 years old) on Days 1, 8, 15, and 22 of a 28-day cycle for Cohort A and Cohort B (for up to 12 cycles).
Initially, 6 participants will be enrolled into each cohort and each will receive 1500 mg durvalumab.
The dose-limiting toxicity (DLT) evaluation period will be the first treatment cycle.
- If ≤ 1 of the 6 initial participants experience a DLT within the first cycle, then the dose expansion phase may be initiated with durvalumab 1500 mg as the recommended dose (RD);
- If 2 or more of the 6 initial participants experience a DLT within the first cycle, then the maximum tolerated dose (MTD) has been exceeded and de-escalation to durvalumab 750 mg level after review of safety and pharmacokinetic/pharmacodynamic (PK/Pd) of the initial 6 participants by the Dose Review Team (DRT).
Any of the cohorts may be removed from the study based on emerging PK, Pd, efficacy or safety data.
Dose de-escalation will only occur after review of safety (DLT) and possibly PK/Pd data by the Dose Review Team ( DRT).
Note: In the US, two treatment arms (A and B) will be enrolled in parallel. Cohort C will enroll upon completion of at least 4 cycles of follow-up for safety assessment of Cohorts A and B.
- Conditions
- Multiple Myeloma
- Being tested
- Durvalumab, Lenalidomide, Dexamethasone
- Keywords
- Open-label, Phase 1/2, Durvalumab, MEDI4736, Lenalidomide (Len), Dexamethasone (dex), Multiple Myeloma, Newly-Diagnosed (NDMM), Transplant Non-eligible (TNE), PD-L1, Durvalumab (DURVA)
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurvalumabDrug
Also called MEDI4736, DUR, DURVA
single use vials administered via intravenous infusion
LenalidomideDrug
Also called LEN, Revlimid
capsules for oral administration
DexamethasoneDrug
Also called corticosteroid, dex
tablets for oral administration
| Study group | Role | What they receive |
|---|---|---|
| Cohort A: High risk, TNE | Experimental | High risk, transplant non-eligible [TNE], newly diagnosed multiple myeloma (NDMM) participants who were administered
* Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle
* Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance [CrCl]) value on Days 1 to 21 of each 28-day treatment cycle
* Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle Receives: Drug: Durvalumab; Drug: Lenalidomide; Drug: Dexamethasone |
| Cohort B: >=65 years old, TNE | Experimental | >= 65 years old, transplant non-eligible [TNE], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered
* Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle
* Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance [CrCl]) value on Days 1 to 21 of each 28-day treatment cycle
* Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles Receives: Drug: Durvalumab; Drug: Lenalidomide; Drug: Dexamethasone |
| Cohort C: High risk, Post-transplant | Experimental | High risk, post-transplant NDMM participants were administered the following as maintenance therapy:
* Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle
* Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle Receives: Drug: Durvalumab; Drug: Lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants With Dose-Limiting Toxicities (DLTs) During the Dose-Determining Timeframe (Day 1 - Day 28)
A Dose Review Team (DRT) evaluated DLTs to determine the recommended dose (RD) of Durvalumab to use in the Expansion Period. A DLT was defined as: a. Grade 4 neutropenia for >= 5 days. b. Grade 3 neutropenia associated with fever (≥ 38.5°C / 101.3°F) of any duration. c. Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or platelets transfusion. d. Grade 4 hematologic toxicity that does not resolve to baseline level <=72 hours. e. Grade 4 anemia, unexplained by underlying disease. f. Any nonhematologic toxicity Grade ≥ 3 except for alopecia and nausea. g. Treatment interruption >= 2 weeks due to AE. If ≤ 1 of the 6 initial participants in each cohort experience a DLT during cycle 1, the RD was Durvalumab 1500 mg; If >=2 of the 6 initial participants in any cohort experience a DLT during cycle 1, the maximum tolerated dose (MTD) was exceeded and the dose level of Durvalumab was de-escalated to 750 mg
Measured: First treatment cycle: Day 1 to Day 28
Secondary outcomes (25)
Participants With Treatment Emergent Adverse Events (TEAE)
An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. A TEAE includes AEs between the first dose date of either study drug and 90 days after the last dose of study drug. A serious AE is any AE occurring at any dose that: • Results in death; • Is life-threatening; • Requires or prolongs existing inpatient hospitalization; • Results in persistent or significant disability/incapacity; • Is a congenital anomaly/birth defect; • Constitutes an important medical event. The Investigator assessed the relationship of each AE to study drug and graded the severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03): - Grade 1 = Mild - Grade 2 = Moderate (some limitation in activity; no/minimal medical intervention required) - Grade 3 = Severe (limitation in activity; medical intervention required) - Grade 4 = Life-threatening - Grade 5 = Death
Measured: Day 1 up to Week 84 (the longer of 90 days after discontinuing treatment with DURVA, or 28 days after the last dose of LEN or dex)
Overall Response Rate (ORR) for Cohorts A and B: Percentage of Participants Who Achieved a Partial Response or Better According to the International Myeloma Working Group (IMWG) Uniform Response Criteria
Tumor response, including progressive disease, was assessed by the investigators and captured the best assessment of response during the treatment period. ORR was defined as partial response (PR) or better which includes PR, very good partial response (VGPR), complete response (CR), or stringent complete response (sCR). A PR required ≥ 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by ≥ 90% or to < 200 mg per 24 hours. If present at baseline, a ≥ 50% reduction in the size of soft tissue plasmacytomas was also required. sCR required - a negative immunofixation of serum and urine and - disappearance of any soft tissue plasmacytomas and - ≤ 5% plasma cells in bone marrow and normal free light-chain (FLC) ratio and - absence of clonal plasma cells by immunohistochemistry or 2- to 4-color flow cytometry.
Measured: Day 1 of each cycle starting with Cycle 2 up to Cycle 17 plus one week for the end of treatment visit (Day 29 up to Week 73)
Response Improvement Rate (RIR) for Cohort C: Percentage of Participants Achieving a Response Improved From Cycle 1 Day 1 as Assessed by the Investigators Using the International Myeloma Working Group (IMWG) Uniform Response Criteria
Response Improvement Rate is defined as the percentage of participants who achieved a response from treatment as compared to the pre-autologous stem cell transplantation [ASCT] diseases measurement used as baseline for response assessment. IMWG response categories could be stable disease (SD), partial response (PR), very good partial response (VGPR), complete response (CR), or stringent complete response (sCR), as long as it represented an improvement compared to prior to transplant.
Measured: Baseline (Cycle 1 Day 1); Treatment: Day 1 of each cycle starting with Cycle 2 up to Cycle 15 plus one week for the end of treatment visit (Day 29 up to Week 61)
Time to Response (for Cohorts A and B)
Time to response (for responders only, per IMWG Uniform Response Criteria) is calculated as the time from the first date of dosing of study medication to the first date of documented response (PR or better).
Measured: Day 1 of each cycle starting with Cycle 2 up to Cycle 17 plus one week for the end of treatment visit (Day 29 up to Week 73)
Kaplan-Meier Estimates for Duration of Response (for Cohort A and B)
Duration of response (for responders only) was defined as the time from earliest date of documented response (PR or better) to the earliest date of disease progression (DP) as determined by the investigator per IMWG Uniform Response criteria or death during study treatment, whichever occurred first.
Measured: Day 1 of each cycle starting with Cycle 2 up to Cycle 17 plus one week for the end of treatment visit (Day 29 up to Week 73)
Durvalumab (DURVA) Serum Pharmacokinetic (PK) Parameters in Cycle 1: Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-last)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.
Measured: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.
Measured: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Maximum Observed Concentration (Cmax)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.
Measured: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Time to Maximum Observed Concentration (Tmax)
Time to maximum observed concentration of Durvalumab (DURVA) after multiple doses on day 1 obtained from the observed concentration versus time data
Measured: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Terminal Elimination Half-life (t1/2)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.
Measured: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Clearance (CL)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.
Measured: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Volume of Distribution (Vz)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.
Measured: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-last)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.
Measured: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.
Measured: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Maximum Observed Concentration (Cmax)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.
Measured: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Time to Maximum Observed Concentration (Tmax)
Time to maximum observed concentration of Lenalidomide (LEN) after multiple doses on day 1 obtained from the observed concentration versus time data
Measured: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Terminal Elimination Half-life (t1/2)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.
Measured: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Apparent Clearance (CL/F)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.
Measured: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Apparent Volume of Distribution (Vz/F)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.
Measured: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma PK Parameters in Cycle 1 Day 15: Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-last)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.
Measured: Cycle 1 Day 15: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 15: Maximum Observed Concentration (Cmax)
Geometric mean was obtained by computing the arithmetic mean of the logarithm-transformed values of concentration/PK parameters and then using the exponentiation to return the computation to the original scales. Geometric CV% was calculated as follows: CV% = 100*SQRT(EXP(σ2)-1), where σ2 denotes the variance of the log-transformed values.
Measured: Cycle 1 Day 15: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 15: Time to Maximum Observed Concentration (Tmax)
Time to maximum observed concentration of Lenalidomide (LEN) after multiple doses on day 15 obtained from the observed concentration versus time data
Measured: Cycle 1 Day 15: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Participants Who Developed Anti-drug Antibody Against Durvalumab
The number of participants who develop antidrug antibody against durvalumab at any of the sampling timepoints during the study.
Measured: Pre-dose samples on Day 1 of cycles 1, 2, 4, 6, 10, and 14 (study days 1, 29, 85, 141, 253, 393)
Participants Who Had Either Disease Progression or Death
This outcome was originally defined as a Kaplan-Meier estimate of progression-free survival (PFS) which estimated the time between first date of dosing of study medication and disease progression, as determined by the investigator using the IMWG Uniform Response Criteria, or death during study treatment, whichever occurred earlier. However due to the early study termination and limited follow-up time, the majority of participants were censored for PFS analysis. Data reported instead represent the number of participants who died during study treatment or had disease progression within 90 days of the last dose of durvalumab.
Measured: Day 1 up to Week 84
Participants Who Died Up To Data Cut-off Date (15 December 2017)
This outcome was originally defined as a Kaplan-Meier estimate of overall survival (OS) and was defined as the time between first date of dosing of study medication and death due to any cause. However due to the early study termination and limited follow-up time, the majority of participants were censored for OS analysis. Data reported instead represent the number of participants who died due to any cause from Day 1 up to data cut-off.
Measured: Day 1 up to Week 87
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2016 (estimated)
- Study start25 Apr 2016
- Primary completion15 Dec 2017
- Study completion6 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by CelgeneThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Celgene
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02685826
- Sponsor's protocol ID
- MEDI4736-MM-002
- Other IDs
- 2015-004831-11, U1111-1179-8722, 2015
- Status last verified
- Sep 2023
- First submitted
- 16 Feb 2016
- Last updated
- 6 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Multicenter, Open-label Study to Determine the Recommended Dose and Regimen of Durvalumab (MEDI4736) in Combination With Lenalidomide (LEN) With and Without Dexamethasone (DEX)in Subjects With Newly Diagnosed Multiple Myeloma (NDMM)
- ClinicalTrials.gov ID
- NCT02685826
- Acronym / sponsor ID
- MEDI4736-MM-002
- Conditions
- Multiple Myeloma
- Keywords
- Open-label, Phase 1/2, Durvalumab, MEDI4736, Lenalidomide (Len), Dexamethasone (dex), Multiple Myeloma, Newly-Diagnosed (NDMM)
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 56 participants (actual)
- Lead sponsor
- CelgeneIndustry (pharma, biotech, devices)
- Study start
- 25 Apr 2016 (actual)
- Primary completion
- 15 Dec 2017 (actual)
- Study completion
- 6 Sep 2022 (actual)
- First posted
- 19 Feb 2016 (estimated)
- Results
- Posted 11 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The dose-finding phase will determine recommended dose (RD) for durvalumab in combination with lenalidomide (LEN) with and without dexamethasone (dex) in a 28-day treatment cycle. Three treatment Cohorts (A, B, and C) will be enrolled in parallel:
- Cohort A: durvalumab + LEN + dex in high risk transplant non-eligible (TNE) newly diagnosed multiple myeloma (NDMM) participants;
- Cohort B: durvalumab + LEN + dex (dex for up to 12 cycles) in ≥ 65 years old TNE NDMM participants who are not high risk;
- Cohort C: durvalumab + LEN as maintenance in post-transplant high risk NDMM participants.
Based on experience with durvalumab for other indications, the initial dose of durvalumab will be 1500 mg for each treatment cohort. The dose of durvalumab might be de-escalated to 750 mg level.
The dose of LEN will be 25 mg (adjustable per the creatinine clearance [CrCl] value) on Days 1 to 21 of each 28-day treatment cycle for participants in Cohort A and B. The dose of LEN will be 10 mg on Days 1 to 21 of each 28-day treatment cycle for participants in Cohort C.
The dose of dex will be 40 mg/day (for participants ≤ 75 years old) or 20 mg/day (for participants > 75 years old) on Days 1, 8, 15, and 22 of a 28-day cycle for Cohort A and Cohort B (for up to 12 cycles).
Initially, 6 participants will be enrolled into each cohort and each will receive 1500 mg durvalumab.
The dose-limiting toxicity (DLT) evaluation period will be the first treatment cycle.
- If ≤ 1 of the 6 initial participants experience a DLT within the first cycle, then the dose expansion phase may be initiated with durvalumab 1500 mg as the recommended dose (RD);
- If 2 or more of the 6 initial participants experience a DLT within the first cycle, then the maximum tolerated dose (MTD) has been exceeded and de-escalation to durvalumab 750 mg level after review of safety and pharmacokinetic/pharmacodynamic (PK/Pd) of the initial 6 participants by the Dose Review Team (DRT).
Any of the cohorts may be removed from the study based on emerging PK, Pd, efficacy or safety data.
Dose de-escalation will only occur after review of safety (DLT) and possibly PK/Pd data by the Dose Review Team ( DRT).
Note: In the US, two treatment arms (A and B) will be enrolled in parallel. Cohort C will enroll upon completion of at least 4 cycles of follow-up for safety assessment of Cohorts A and B.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A: High risk, TNE | Experimental | Drug: Durvalumab, Drug: Lenalidomide, Drug: DexamethasoneHigh risk, transplant non-eligible [TNE], newly diagnosed multiple myeloma (NDMM) participants who were administered * Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle * Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance [CrCl]) value on Days 1 to 21 of each 28-day treatment cycle * Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle |
| Cohort B: >=65 years old, TNE | Experimental | Drug: Durvalumab, Drug: Lenalidomide, Drug: Dexamethasone>= 65 years old, transplant non-eligible [TNE], newly diagnosed multiple myeloma (NDMM) participants who were not high risk were administered * Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle * Oral lenalidomide (LEN) 25 mg/day (adjust per the creatinine clearance [CrCl]) value on Days 1 to 21 of each 28-day treatment cycle * Oral dexamethasone (dex) 40 mg/day (≤ 75 years old) or 20 mg/day (> 75 years old) on Days 1, 8, 15, and 22 of each 28-day cycle, up to 12 cycles |
| Cohort C: High risk, Post-transplant | Experimental | Drug: Durvalumab, Drug: LenalidomideHigh risk, post-transplant NDMM participants were administered the following as maintenance therapy: * Intravenous (IV) durvalumab at 1500 mg on Day 1 of each 28-day cycle * Oral lenalidomide (LEN) 10 mg/day on Days 1 to 21 of each 28-day treatment cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (44 listed)
- Subjects must satisfy the following criteria to be enrolled into the study:
- 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:
Key exclusion criteria (42 listed)
- The presence of any of the following will exclude a subject from enrollment:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DurvalumabAlso: MEDI4736, DUR, DURVAsingle use vials administered via intravenous infusion | Drug | Cohort A: High risk, TNE, Cohort B: >=65 years old, TNE, Cohort C: High risk, Post-transplant |
| LenalidomideAlso: LEN, Revlimidcapsules for oral administration | Drug | Cohort A: High risk, TNE, Cohort B: >=65 years old, TNE, Cohort C: High risk, Post-transplant |
| DexamethasoneAlso: corticosteroid, dextablets for oral administration | Drug | Cohort A: High risk, TNE, Cohort B: >=65 years old, TNE |
Primary outcome
Participants With Dose-Limiting Toxicities (DLTs) During the Dose-Determining Timeframe (Day 1 - Day 28)
Time frame: First treatment cycle: Day 1 to Day 28
A Dose Review Team (DRT) evaluated DLTs to determine the recommended dose (RD) of Durvalumab to use in the Expansion Period. A DLT was defined as: a. Grade 4 neutropenia for >= 5 days. b. Grade 3 neutropenia associated with fever (≥ 38.5°C / 101.3°F) of any duration. c. Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding, or platelets transfusion. d. Grade 4 hematologic toxicity that does not resolve to baseline level <=72 hours. e. Grade 4 anemia, unexplained by underlying disease. f. Any nonhematologic toxicity Grade ≥ 3 except for alopecia and nausea. g. Treatment interruption >= 2 weeks due to AE. If ≤ 1 of the 6 initial participants in each cohort experience a DLT during cycle 1, the RD was Durvalumab 1500 mg; If >=2 of the 6 initial participants in any cohort experience a DLT during cycle 1, the maximum tolerated dose (MTD) was exceeded and the dose level of Durvalumab was de-escalated to 750 mg
25 secondary outcomes
Participants With Treatment Emergent Adverse Events (TEAE)
Time frame: Day 1 up to Week 84 (the longer of 90 days after discontinuing treatment with DURVA, or 28 days after the last dose of LEN or dex)
Overall Response Rate (ORR) for Cohorts A and B: Percentage of Participants Who Achieved a Partial Response or Better According to the International Myeloma Working Group (IMWG) Uniform Response Criteria
Time frame: Day 1 of each cycle starting with Cycle 2 up to Cycle 17 plus one week for the end of treatment visit (Day 29 up to Week 73)
Response Improvement Rate (RIR) for Cohort C: Percentage of Participants Achieving a Response Improved From Cycle 1 Day 1 as Assessed by the Investigators Using the International Myeloma Working Group (IMWG) Uniform Response Criteria
Time frame: Baseline (Cycle 1 Day 1); Treatment: Day 1 of each cycle starting with Cycle 2 up to Cycle 15 plus one week for the end of treatment visit (Day 29 up to Week 61)
Time to Response (for Cohorts A and B)
Time frame: Day 1 of each cycle starting with Cycle 2 up to Cycle 17 plus one week for the end of treatment visit (Day 29 up to Week 73)
Kaplan-Meier Estimates for Duration of Response (for Cohort A and B)
Time frame: Day 1 of each cycle starting with Cycle 2 up to Cycle 17 plus one week for the end of treatment visit (Day 29 up to Week 73)
Durvalumab (DURVA) Serum Pharmacokinetic (PK) Parameters in Cycle 1: Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-last)
Time frame: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf)
Time frame: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Maximum Observed Concentration (Cmax)
Time frame: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Time to Maximum Observed Concentration (Tmax)
Time frame: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Terminal Elimination Half-life (t1/2)
Time frame: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Clearance (CL)
Time frame: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
Durvalumab (DURVA) Serum PK Parameters in Cycle 1: Volume of Distribution (Vz)
Time frame: pre-infusion (-60 to -5 minutes prior to dose), end of infusion (EOI), 4 hours, 168 hours (Day 8), 336 hours (Day 15) and 504 hours (Day 22) after administration of DURVA on Day 1
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-last)
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf)
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Maximum Observed Concentration (Cmax)
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Time to Maximum Observed Concentration (Tmax)
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Terminal Elimination Half-life (t1/2)
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Apparent Clearance (CL/F)
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 1: Apparent Volume of Distribution (Vz/F)
Time frame: Cycle 1 Day 1: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma PK Parameters in Cycle 1 Day 15: Area Under the Concentration-time Curve From Time Zero to the Last Measured Time Point (AUC0-last)
Time frame: Cycle 1 Day 15: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 15: Maximum Observed Concentration (Cmax)
Time frame: Cycle 1 Day 15: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Lenalidomide (LEN) Plasma Pharmacokinetic (PK) Parameters in Cycle 1 Day 15: Time to Maximum Observed Concentration (Tmax)
Time frame: Cycle 1 Day 15: pre-dose, 0.5, 1, 2, 4, and 8 hours post LEN dose
Participants Who Developed Anti-drug Antibody Against Durvalumab
Time frame: Pre-dose samples on Day 1 of cycles 1, 2, 4, 6, 10, and 14 (study days 1, 29, 85, 141, 253, 393)
Participants Who Had Either Disease Progression or Death
Time frame: Day 1 up to Week 84
Participants Who Died Up To Data Cut-off Date (15 December 2017)
Time frame: Day 1 up to Week 87
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BMS Clinical Trial InformationLink provided by the sponsor.
- BMS Clinical Trial Patient RecruitingLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
54 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Durvalumab, Lenalidomide and Dexamethasone in people with Multiple Myeloma, run by Celgene at 54 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 44 inclusion and 42 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 54 sites in Spain, Italy, Canada, United States, Denmark and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participants With Dose-Limiting Toxicities (DLTs) During the Dose-Determining Timeframe (Day 1 - Day 28) (time frame: First treatment cycle: Day 1 to Day 28). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2023.