Clinical Trials /

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

NCT02685826

Description:

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. ****************************************************************************** On 05 Sep 2017, Study MEDI4736-MM-002 was prematurely interrupted as a result of a Full Clinical Hold placed by the United States Food and Drug Administration (US FDA). The decision by the FDA was based on data related to risks of the anti-PD-1 antibody, pembrolizumab, in combination with immunomodulatory drugs in patients with MM observed in non-Celgene sponsored clinical trials. As a result of the Full Clinical Hold, all participants were discontinued from all study treatments (durvalumab, LEN and/or dex). These participants then proceeded with the End of Trial and safety follow-up visits as per protocol. The last visit for the last subject occurred on the 15 Dec 2017 however, participants will continue to be followed for survival and second primary malignancies until approximately September 2022.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of Durvalumab in Combination With Lenalidomide With and Without Dexamethasone in Adults With Newly Diagnosed Multiple Myeloma
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: MEDI4736-MM-002
  • SECONDARY ID: 2015-004831-11
  • NCT ID: NCT02685826

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
DurvalumabMEDI4736, DUR, DURVACohort A: High risk, TNE
LenalidomideLEN, RevlimidCohort A: High risk, TNE
Dexamethasonecorticosteroid, dexCohort A: High risk, TNE

Purpose

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. ****************************************************************************** On 05 Sep 2017, Study MEDI4736-MM-002 was prematurely interrupted as a result of a Full Clinical Hold placed by the United States Food and Drug Administration (US FDA). The decision by the FDA was based on data related to risks of the anti-PD-1 antibody, pembrolizumab, in combination with immunomodulatory drugs in patients with MM observed in non-Celgene sponsored clinical trials. As a result of the Full Clinical Hold, all participants were discontinued from all study treatments (durvalumab, LEN and/or dex). These participants then proceeded with the End of Trial and safety follow-up visits as per protocol. The last visit for the last subject occurred on the 15 Dec 2017 however, participants will continue to be followed for survival and second primary malignancies until approximately September 2022.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort A: High risk, TNEExperimentalHigh 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
  • Durvalumab
  • Lenalidomide
  • Dexamethasone
Cohort B: >=65 years old, TNEExperimental>= 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
  • Durvalumab
  • Lenalidomide
  • Dexamethasone
Cohort C: High risk, Post-transplantExperimentalHigh 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
  • Durvalumab
  • Lenalidomide

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects must satisfy the following criteria to be enrolled into the study:

               1. Subject is ≥ 18 years of age at the time of signing the informed consent form
                  (ICF)

               2. Subject must understand and voluntarily sign an ICF prior to any study-related
                  assessments/procedures being conducted

               3. Subject is willing and able to adhere to the study visit schedule and other
                  protocol requirements

               4. 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:

             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:

             a. 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.

             b. 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.

             c. Refrain from egg cell and blood donation for 90 days after the final dose of
             durvalumab.

             7. Male subjects must :

             a. 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.

             b. 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:

             a. 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

             b. International Staging System (ISS) Stage III; or

             c. 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:

               1. Have a post-transplant response as Partial response (PR) or better at the time of
                  enrollment to this study;

               2. 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;

             c. 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

        Exclusion Criteria:

          -  The presence of any of the following will exclude a subject from enrollment:

               1. 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)

               2. Any of the following laboratory abnormalities:

                    1. Absolute neutrophil count (ANC) < 1,000/μL

                    2. Untransfused platelet count < 75,000 cells/μL

                    3. Serum aspartate aminotransferase/serum glutamic oxaloacetic transaminase
                       (SGOT/AST) or alanine aminotransferase (SGPT/ALT) > 2.5*upper limit of
                       normal (ULN)

                    4. Serum total bilirubin > 1.5*ULN or > 3.0 mg/dL for subjects with documented
                       Gilbert's syndrome

                    5. Corrected serum calcium >13.5 mg/dL (> 3.4 mmol/L)

               3. Renal failure requiring hemodialysis or peritoneal dialysis

               4. 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

               5. Peripheral neuropathy ≥ Grade 2

               6. Primary AL (immunoglobulin light-chain) amyloidosis and myeloma complicated by
                  amyloidosis

               7. 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:

                    1. Basal cell carcinoma of the skin

                    2. Squamous cell carcinoma of the skin

                    3. Carcinoma in situ of the cervix

                    4. Carcinoma in situ of the breast

                    5. Incidental histologic finding of prostate cancer (T1a or T1b using the TNM
                       [tumor, nodes, metastasis] clinical staging system) or prostate cancer that
                       is curative

               8. Subjects is positive for human immunodeficiency virus (HIV); chronic or active
                  hepatitis B or active hepatitis A, or C

               9. 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

              10. Subjects has history of organ or allogeneic stem cell transplantation

              11. 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

              12. Known or suspected hypersensitivity to the excipients contained in the
                  formulation of durvalumab, lenalidomide, or dexamethasone

              13. Major surgery (as defined by the investigator) within the 28 days prior to the
                  first dose of study treatment

              14. Received prior treatment (for any reason)with a monoclonal antibody within 5
                  half-lives of initiating study treatment

              15. Use of any investigational agents within 28 days or 5 half-lives (whichever is
                  longer) of initiating study treatment

              16. 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:

                    1. Intranasal, inhaled, topical or local steroid injections (eg,
                       intra-articular injection);

                    2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of
                       prednisone or equivalent;

                    3. Steroids as premedication for hypersensitivity reactions (eg, computed
                       tomography (CT) scan premedication);

              17. 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:

                    1. Subjects with vitiligo or alopecia;

                    2. Subjects with hypothyroidism (eg, following Hashimoto syndrome) stable on
                       hormone replacement; or

                    3. Subjects with psoriasis not requiring systemic treatment;

              18. History of primary immunodeficiency

              19. Subject has incidence of gastrointestinal disease that may significantly alter
                  the absorption of LEN

              20. Receipt of live, attenuated vaccine within 30 days prior to the first dose of
                  durvalumab

              21. 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)

              22. Females who are pregnant, nursing or breastfeeding, or intend to become pregnant
                  during the participation to the study

              23. Any significant medical condition, laboratory abnormality, or psychiatric illness
                  that would prevent the subject from participating in the study

              24. Any condition including the presence of laboratory abnormalities, which places
                  the subject at unacceptable risk if he/she were to participate in the study

              25. Any condition that confounds the ability to interpret data from the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description:A Dose Review Team (DRT) evaluated DLTs and, if applicable, other data to determine the recommended dose (RD) of durvalmab to use in the Expansion Period. The DRT included sponsor personnel, investigators and outside consultants. 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

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description: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
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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).
Measure: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)
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.
Measure:Lenalidoide (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
Safety Issue:
Description: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.
Measure:Lenalidoide (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
Safety Issue:
Description: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.
Measure:Lenalidoide (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
Safety Issue:
Description: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.
Measure:Lenalidoide (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
Safety Issue:
Description:
Measure:Lenalidoide (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
Safety Issue:
Description: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.
Measure:Lenalidoide (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
Safety Issue:
Description: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.
Measure:Lenalidoide (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
Safety Issue:
Description: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.
Measure:Lenalidomide 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
Safety Issue:
Description: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.
Measure:Lenalidoide (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
Safety Issue:
Description: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.
Measure:Lenalidoide (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
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:The number of participants who develop antidrug antibody against durvalumab at any of the sampling timepoints during the study.
Measure:Participants Who Had Either Disease Progression or Death
Time Frame:Day 1 up to Week 84
Safety Issue:
Description: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.
Measure:Participants Who Died Up To Data Cut-off Date (15 December 2017)
Time Frame:Day 1 up to Week 87
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Celgene

Trial 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)

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